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{{short description|Hormone involved in stomach, pancreas and liver secretions}}{{#invoke:Infobox_gene|getTemplateData|QID=Q14820612}}'''Secretin''' is a [[hormone]] that regulates [[Osmoregulation|water homeostasis]] throughout the body and influences the environment of the [[duodenum]] by regulating secretions in the [[stomach]], [[pancreas]], and [[liver]]. It is a [[peptide hormone]] produced in the [[S cell]]s of the duodenum, which are located in the [[intestinal gland]]s.<ref name="pmid7000396">{{cite journal | vauthors = Häcki WH | title = Secretin | journal = Clinics in Gastroenterology | volume = 9 | issue = 3 | pages = 609–632 | date = September 1980 | pmid = 7000396 | doi = 10.1016/S0300-5089(21)00474-0 }}</ref> In humans, the secretin peptide is encoded by the ''SCT'' [[gene]].<ref name="pmid2315322">{{cite journal | vauthors = Kopin AS, Wheeler MB, Leiter AB | title = Secretin: structure of the precursor and tissue distribution of the mRNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 6 | pages = 2299–2303 | date = March 1990 | pmid = 2315322 | pmc = 53674 | doi = 10.1073/pnas.87.6.2299 | bibcode = 1990PNAS...87.2299K | doi-access = free | jstor = 2354038 }}</ref>
{{short description|Hormone involved in stomach, pancreas and liver secretions}}
{{Infobox_gene}}


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Secretin helps regulate the [[pH]] of the duodenum by inhibiting the secretion of [[gastric acid]] from the [[parietal cells]] of the stomach and stimulating the production of [[bicarbonate]] from the [[ductal cells]] of the pancreas.<ref name="pmid11060443">{{cite journal | vauthors = Whitmore TE, Holloway JL, Lofton-Day CE, Maurer MF, Chen L, Quinton TJ, Vincent JB, Scherer SW, Lok S | display-authors = 6 | title = Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA | journal = Cytogenetics and Cell Genetics | volume = 90 | issue = 1–2 | pages = 47–52 | year = 2000 | pmid = 11060443 | doi = 10.1159/000015658 | s2cid = 12850155 }}</ref><ref>{{Cite book|title=Physiology|author=Costanzo, Linda S.|date=2006|publisher=Saunders Elsevier|isbn=9781416023203|edition= 3rd |location=Philadelphia, PA|oclc=62326921}}</ref> It also stimulates the secretion of bicarbonate and water by [[cholangiocyte]]s in the bile duct, protecting it from [[bile acids]] by controlling the pH and promoting the flow in the duct.<ref name="Banales2019">{{cite journal | vauthors = Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ | title = Cholangiocyte pathobiology | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 16 | issue = 5 | pages = 269–281 | date = May 2019 | pmid = 30850822 | pmc = 6563606 | doi = 10.1038/s41575-019-0125-y }}</ref> Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, [[cholecystokinin]] (CCK), stimulates the [[gallbladder]] to contract, delivering its stored bile.
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'''Secretin''' is a [[hormone]] that regulates [[Osmoregulation|water homeostasis]] throughout the body and influences the environment of the [[duodenum]] by regulating secretions in the [[stomach]], [[pancreas]], and [[liver]]. It is a [[peptide hormone]] produced in the [[S cell]]s of the duodenum, which are located in the [[intestinal gland]]s.<ref name="pmid7000396">{{cite journal |vauthors=Häcki WH |title=Secretin |journal=Clinics in Gastroenterology |volume=9 |issue=3 |pages=609–32 |year=1980 |doi=10.1016/S0300-5089(21)00474-0 |pmid=7000396 }}</ref> In humans, the secretin peptide is encoded by the SCT [[gene]].<ref name="pmid2315322">{{cite journal |vauthors=Kopin AS, Wheeler MB, Leiter AB |title=Secretin: structure of the precursor and tissue distribution of the mRNA |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=87 |issue=6 |pages=2299–303 |year=1990 |pmid=2315322 |pmc=53674 |jstor=2354038 |bibcode=1990PNAS...87.2299K |doi=10.1073/pnas.87.6.2299 |doi-access=free }}</ref>


'''Prosecretin''' is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by [[gastric acid]]. This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid.<ref>{{cite journal | vauthors = Gafvelin G, Jörnvall H, Mutt V | title = Processing of prosecretin: isolation of a secretin precursor from porcine intestine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 17 | pages = 6781–6785 | date = September 1990 | pmid = 2395872 | pmc = 54621 | doi = 10.1073/pnas.87.17.6781 | doi-access = free | bibcode = 1990PNAS...87.6781G }}</ref>
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Secretin helps regulate the [[pH]] of the duodenum by (1) inhibiting the secretion of [[gastric acid]] from the [[parietal cells]] of the stomach and (2) stimulating the production of [[bicarbonate]] from the ductal cells of the pancreas.<ref name="pmid11060443">{{cite journal |vauthors=Whitmore TE, Holloway JL, Lofton-Day CE, Maurer MF, Chen L, Quinton TJ, Vincent JB, Scherer SW, Lok S |title=Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA |journal=Cytogenetics and Cell Genetics |volume=90 |issue=1–2 |pages=47–52 |year=2000 |pmid=11060443 |doi=10.1159/000015658 |s2cid=12850155 }}</ref><ref>{{Cite book|title=Physiology|author=Costanzo, Linda S.|date=2006|publisher=Saunders Elsevier|isbn=9781416023203|edition= 3rd |location=Philadelphia, PA|oclc=62326921}}</ref> It also stimulates the secretion of bicarbonate and water by [[cholangiocyte]]s in the bile duct, protecting it from [[bile acids]] by controlling the pH and promoting the flow in the duct.<ref name="Banales2019">{{Cite journal |vauthors=Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ |date=2019 |title=Cholangiocyte pathobiology |journal=Nature Reviews Gastroenterology & Hepatology |language=en |volume=16 |issue=5 |pages=269–281 |doi=10.1038/s41575-019-0125-y |issn=1759-5045 |pmc=6563606 |pmid=30850822}}</ref> Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, [[cholecystokinin]] (CCK), is stimulating the [[gallbladder]] to contract, delivering its stored bile.


'''Prosecretin''' is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by [[gastric acid]]. This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid.<ref>{{cite journal | vauthors = Gafvelin G, Jörnvall H, Mutt V | title = Processing of prosecretin: isolation of a secretin precursor from porcine intestine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 17 | pages = 6781–5 | date = Sep 1990 | pmid = 2395872 | pmc = 54621 | doi = 10.1073/pnas.87.17.6781 | url = http://www.pnas.org/content/87/17/6781.full.pdf | bibcode = 1990PNAS...87.6781G | doi-access = free }}</ref>
In 2007, secretin was discovered to play a role in [[osmoregulation]] by acting on the [[hypothalamus]], [[pituitary|pituitary gland]], and [[kidney]].<ref name="Chu07">{{cite journal | vauthors = Chu JY, Chung SC, Lam AK, Tam S, Chung SK, Chow BK | title = Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption | journal = Molecular and Cellular Biology | volume = 27 | issue = 7 | pages = 2499–2511 | date = April 2007 | pmid = 17283064 | pmc = 1899889 | doi = 10.1128/MCB.01088-06 }}</ref><ref name="Chu">{{cite journal | vauthors = Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK | title = Secretin as a neurohypophysial factor regulating body water homeostasis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 37 | pages = 15961–15966 | date = September 2009 | pmid = 19805236 | pmc = 2747226 | doi = 10.1073/pnas.0903695106 | bibcode = 2009PNAS..10615961C | doi-access = free | jstor = 40484830 }}</ref>


== History ==
In 2007, secretin was discovered to play a role in [[osmoregulation]] by acting on the [[hypothalamus]], [[pituitary|pituitary gland]], and [[kidney]].<ref name="Chu07">{{cite journal |vauthors=Chu JY, Chung SC, Lam AK, Tam S, Chung SK, Chow BK |title=Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption |journal=Molecular and Cellular Biology |volume=27 |issue=7 |pages=2499–511 |year=2007 |pmid=17283064 |pmc=1899889 |doi=10.1128/MCB.01088-06 }}</ref><ref name="Chu">{{cite journal |vauthors=Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK |title=Secretin as a neurohypophysial factor regulating body water homeostasis |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 |issue=37 |pages=15961–6 |year=2009 |pmid=19805236 |pmc=2747226 |jstor=40484830 |bibcode=2009PNAS..10615961C |doi=10.1073/pnas.0903695106 |doi-access=free }}</ref>
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In 1902, [[William Bayliss]] and [[Ernest Starling]] were studying how the nervous system controls the process of digestion.<ref name="Bayliss_1902">{{cite journal | vauthors = Bayliss WM, Starling EH | title = The mechanism of pancreatic secretion | journal = The Journal of Physiology | volume = 28 | issue = 5 | pages = 325–353 | date = September 1902 | pmid = 16992627 | pmc = 1540572 | doi = 10.1113/jphysiol.1902.sp000920 }}</ref> It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion ''secretin''. This type of 'chemical messenger' substance is now called a [[hormone]], a term coined by Starling in 1905.<ref name="pmid_15308687">{{cite journal | vauthors = Hirst BH | title = Secretin and the exposition of hormonal control | journal = The Journal of Physiology | volume = 560 | issue = Pt 2 | pages = 339 | date = October 2004 | pmid = 15308687 | pmc = 1665254 | doi = 10.1113/jphysiol.2004.073056 }}</ref>


Secretin is frequently erroneously stated to have been the first hormone identified.<ref>{{cite journal | vauthors = Henriksen JH, Schaffalitzky de Muckadell OB | title = [Secretin--the first hormone] | language = da | journal = Ugeskrift for Laeger | volume = 164 | issue = 3 | pages = 320–325 | date = January 2002 | pmid = 11816326 | trans-title = Secretin--the first hormone | id = {{INIST|13419424}} }}</ref> However, British researchers [[George Oliver (physician)|George Oliver]] and [[Edward_Albert_Sharpey-Schafer|Edward Albert Schäfer]] had already published their findings of an adrenal extract increasing blood pressure and heart rate in brief reports in 1894 and a full publication in 1895, making [[adrenaline]] the first discovered hormone.<ref>{{cite journal | vauthors = Oliver G, Schäfer EA | title = The Physiological Effects of Extracts of the Suprarenal Capsules | journal = The Journal of Physiology | volume = 18 | issue = 3 | pages = 230–276 | date = July 1895 | pmid = 16992252 | doi = 10.1113/jphysiol.1895.sp000564 | pmc = 1514629 }}</ref><ref>{{cite journal | vauthors = Oliver G, Schäfer EA | title = The Physiological Effects of Extracts of the Suprarenal Capsules | journal = The Journal of Physiology | volume = 18 | issue = 3 | pages = 230–276 | date = July 1895 | pmid = 16992252 | pmc = 1514629 | doi = 10.1113/jphysiol.1895.sp000564 }}</ref>
==Discovery ==
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Secretin was the first hormone to be identified.<ref>{{cite journal |vauthors=Henriksen JH, Schaffalitzky de Muckadell OB |title=Sekretin - det første hormon |trans-title=Secretin--the first hormone |language=da |journal=Ugeskrift for Laeger |volume=164 |issue=3 |pages=320–5 |year=2002 |id={{INIST|13419424}} |pmid=11816326 }}</ref> In 1902, [[William Bayliss]] and [[Ernest Starling]] were studying how the nervous system controls the process of digestion.<ref name="Bayliss_1902">{{cite journal |vauthors=Bayliss WM, Starling EH |title=The mechanism of pancreatic secretion |journal=The Journal of Physiology |volume=28 |issue=5 |pages=325–53 |year=1902 |pmid=16992627 |pmc=1540572 |doi=10.1113/jphysiol.1902.sp000920 }}</ref> It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion ''secretin''. Secretin was the first such "chemical messenger" identified. This type of substance is now called a [[hormone]], a term coined by Starling in 1905.<ref name="pmid_15308687">{{Citation |last=Hirst |first=BH |year=2004 |title=Secretin and the exposition of hormonal control |journal=J Physiol |volume=560 |issue=2 |pages=339 |pmid=15308687 |pmc=1665254 |doi=10.1113/jphysiol.2004.073056 |postscript=.}}</ref>


==Structure==
== Structure ==
Secretin is initially synthesized as a 120 amino acid precursor protein known as [[prosecretin]]. This precursor contains an [[N-terminus|N-terminal]] signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid [[C-terminus|C-terminal]] peptide.<ref name="pmid2315322"/>
Secretin is initially synthesized as a 120 amino acid precursor protein known as [[prosecretin]]. This precursor contains an [[N-terminus|N-terminal]] signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid [[C-terminus|C-terminal]] peptide.<ref name="pmid2315322"/>


The mature secretin peptide is a linear [[peptide hormone]], which is composed of 27 [[amino acids]] and has a [[molecular weight]] of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of [[glucagon]], [[vasoactive intestinal peptide]] (VIP), and [[gastric inhibitory peptide]] (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP.<ref name="isbn0-7216-9398-9">{{cite book |last1=Williams |first1=Robert L. |title=Textbook of Endocrinology |publisher=Saunders |location=Philadelphia |year=1981 |page=[https://archive.org/details/textbookofendocre6will/page/697 697] |isbn=978-0-7216-9398-9 |url=https://archive.org/details/textbookofendocre6will/page/697 }}</ref>
The mature secretin peptide is a linear [[peptide hormone]], which is composed of 27 [[amino acids]] and has a [[molecular weight]] of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of [[glucagon]], [[vasoactive intestinal peptide]] (VIP), and [[gastric inhibitory peptide]] (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP.<ref name="isbn0-7216-9398-9">{{cite book | vauthors = Williams RL |title=Textbook of Endocrinology |publisher=Saunders |location=Philadelphia |year=1981 |page=[https://archive.org/details/textbookofendocre6will/page/697 697] |isbn=978-0-7216-9398-9 |url=https://archive.org/details/textbookofendocre6will/page/697 }}</ref>


Secretin also has an amidated [[carboxyl-terminal]] amino acid which is valine.<ref name="isbn0-7216-2888-5">{{cite book |last1=DeGroot |first1=Leslie Jacob |editor1-first=J. E. |editor1-last=McGuigan |title=Endocrinology |publisher=Saunders |location=Philadelphia |year=1989 |pages=[https://archive.org/details/endocrinology0002unse/page/2748 2748] |isbn=978-0-7216-2888-2 |url=https://archive.org/details/endocrinology0002unse/page/2748 }}</ref> The sequence of amino acids in secretin is H–[[Histidine|His]]-[[Serine|Ser]]-[[Aspartic acid|Asp]]-[[Glycine|Gly]]-[[Threonine|Thr]]-[[Phenylalanine|Phe]]-[[Threonine|Thr]]-[[Serine|Ser]]-[[Glutamic acid|Glu]]-[[Leucine|Leu]]-[[Serine|Ser]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Arginine|Arg]]-[[Aspartic acid|Asp]]-[[Serine|Ser]]-[[Alanine|Ala]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Glutamine|Gln]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Leucine|Leu]]-[[Glutamine|Gln]]-[[Glycine|Gly]]-[[Leucine|Leu]]-[[Valine|Val]]–NH<sub>2</sub>.<ref name="isbn0-7216-2888-5"/>
Secretin also has an amidated [[carboxyl-terminal]] amino acid which is valine.<ref name="isbn0-7216-2888-5">{{cite book | vauthors = DeGroot LJ | veditors = McGuigan JE |title=Endocrinology |publisher=Saunders |location=Philadelphia |year=1989 |pages=[https://archive.org/details/endocrinology0002unse/page/2748 2748] |isbn=978-0-7216-2888-2 |url=https://archive.org/details/endocrinology0002unse/page/2748 }}</ref> The sequence of amino acids in secretin is H–[[Histidine|His]]-[[Serine|Ser]]-[[Aspartic acid|Asp]]-[[Glycine|Gly]]-[[Threonine|Thr]]-[[Phenylalanine|Phe]]-[[Threonine|Thr]]-[[Serine|Ser]]-[[Glutamic acid|Glu]]-[[Leucine|Leu]]-[[Serine|Ser]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Arginine|Arg]]-[[Aspartic acid|Asp]]-[[Serine|Ser]]-[[Alanine|Ala]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Glutamine|Gln]]-[[Arginine|Arg]]-[[Leucine|Leu]]-[[Leucine|Leu]]-[[Glutamine|Gln]]-[[Glycine|Gly]]-[[Leucine|Leu]]-[[Valine|Val]]–NH<sub>2</sub>.<ref name="isbn0-7216-2888-5"/>


==Physiology==
==Physiology==


===Production and secretion===
===Production and secretion===
Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the [[mucosa]] of the [[duodenum]], and in smaller numbers in the jejunum of the [[small intestine]].<ref name="pmid4945081">{{cite journal |vauthors=Polak JM, Coulling I, Bloom S, Pearse AG |title=Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa |journal=Scandinavian Journal of Gastroenterology |volume=6 |issue=8 |pages=739–44 |year=1971 |pmid=4945081 |doi=10.3109/00365527109179946 }}</ref>
Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the [[mucosa]] of the [[duodenum]], and in smaller numbers in the [[jejunum]] of the [[small intestine]].<ref name="pmid4945081">{{cite journal | vauthors = Polak JM, Coulling I, Bloom S, Pearse AG | title = Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa | journal = Scandinavian Journal of Gastroenterology | volume = 6 | issue = 8 | pages = 739–744 | year = 1971 | pmid = 4945081 | doi = 10.3109/00365527109179946 }}</ref>


Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species; the acidity is due to [[hydrochloric acid]] in the [[chyme]] that enters the duodenum from the stomach via the [[pyloric sphincter]].<ref name="isbn0-07-022001-8">{{cite book |last1=Frohman |first1=Lawrence A. |last2=Felig |first2=Philip |editor1-first=P. K. |editor1-last=Ghosh |editor2-first=T. M. |editor2-last=O'Dorisio |title=Endocrinology & metabolism |publisher=McGraw-Hill, Medical Pub. Div |location=New York |year=2001 |chapter=Gastrointestinal Hormones and Carcinoid Syndrome |pages=1675–701 |isbn=978-0-07-022001-0 }}</ref> Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.<ref name="ISBN 0-07-140236-5">{{cite book |first1=William F. |last1=Ganong |title=Review of Medical Physiology |edition= 21st |publisher=McGraw-Hill, Medical Pub. Div |location=New York |year=2003 |chapter=Regulation of Gastrointestinal Function |isbn=978-0-07-140236-1 }}{{page needed|date=January 2016}}</ref>
Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species; the acidity is due to [[hydrochloric acid]] in the [[chyme]] that enters the duodenum from the stomach via the [[pyloric sphincter]].<ref name="isbn0-07-022001-8">{{cite book | vauthors = Frohman LA, Felig P | veditors = Ghosh PK, O'Dorisio TM |title=Endocrinology & metabolism |publisher=McGraw-Hill, Medical Pub. Div |location=New York |year=2001 |chapter=Gastrointestinal Hormones and Carcinoid Syndrome |pages=1675–701 |isbn=978-0-07-022001-0 }}</ref> Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.<ref name="ISBN 0-07-140236-5">{{cite book | vauthors = Ganong WF |title=Review of Medical Physiology |edition= 21st |publisher=McGraw-Hill, Medical Pub. Div |location=New York |year=2003 |chapter=Regulation of Gastrointestinal Function |isbn=978-0-07-140236-1 }}{{page needed|date=January 2016}}</ref>


Secretin release is inhibited by [[H2 antagonist|H<sub>2</sub> antagonist]]s, which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released.<ref name="pmid7249893">{{cite journal |vauthors=Rominger JM, Chey WY, Chang TM |title=Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases |journal=Digestive Diseases and Sciences |volume=26 |issue=7 |pages=591–7 |year=1981 |pmid=7249893 |doi=10.1007/BF01367670 |s2cid=7039025 }}</ref>
Secretin release is inhibited by [[H2 antagonist|H<sub>2</sub> antagonist]]s, which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released.<ref name="pmid7249893">{{cite journal | vauthors = Rominger JM, Chey WY, Chang TM | title = Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases | journal = Digestive Diseases and Sciences | volume = 26 | issue = 7 | pages = 591–597 | date = July 1981 | pmid = 7249893 | doi = 10.1007/BF01367670 | s2cid = 7039025 }}</ref>


===Function===
=== Function ===
====pH regulation====
====pH regulation====
Secretin primarily functions to neutralize the pH in the [[duodenum]], allowing digestive [[enzyme]]s from the pancreas (e.g., [[pancreatic amylase]] and [[pancreatic lipase]]) to function optimally.<ref name="isbn0-7216-0240-1"/>
Secretin primarily functions to neutralize the pH in the [[duodenum]], allowing digestive [[enzyme]]s from the pancreas (e.g., [[pancreatic amylase]] and [[pancreatic lipase]]) to function optimally.<ref name="isbn0-7216-0240-1"/>


Secretin targets the [[pancreas]]; pancreatic centroacinar cells have [[secretin receptors]] in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts [[Adenosine triphosphate|ATP]] to [[cyclic AMP]].<ref name="isbn">{{cite book |last1=Gardner |first1=JD |editor1-last=Sleisenger |editor1-first=MH |editor2-last=Fordtran |editor2-first=JS |title=Gastrointestinal Disease |edition= 2nd |publisher=WB Saunders Company |location=Philadelphia |year=1978 |chapter=Receptors and gastrointestinal hormones |pages=179–95 }}</ref> Cyclic AMP acts as second messenger in intracellular signal transduction and causes the organ to secrete a [[bicarbonate]]-rich fluid that flows into the [[intestine]]. Bicarbonate is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine.<ref name="pmid631638">{{cite journal |vauthors=Osnes M, Hanssen LE, Flaten O, Myren J |title=Exocrine pancreatic secretion and immunoreactive secretin (IRS) release after intraduodenal instillation of bile in man |journal=Gut |volume=19 |issue=3 |pages=180–4 |year=1978 |pmid=631638 |pmc=1411891 |doi=10.1136/gut.19.3.180 }}</ref>
Secretin targets the [[pancreas]]; pancreatic centroacinar cells have [[secretin receptors]] in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts [[Adenosine triphosphate|ATP]] to [[cyclic AMP]].<ref name="isbn">{{cite book | vauthors = Gardner JD | veditors = Sleisenger MH, Fordtran JS |title=Gastrointestinal Disease |edition= 2nd |publisher=WB Saunders Company |location=Philadelphia |year=1978 |chapter=Receptors and gastrointestinal hormones |pages=179–95 }}</ref> Cyclic AMP acts as second messenger in intracellular signal transduction and causes the organ to secrete a [[bicarbonate]]-rich fluid that flows into the [[intestine]]. Bicarbonate is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine.<ref name="pmid631638">{{cite journal | vauthors = Osnes M, Hanssen LE, Flaten O, Myren J | title = Exocrine pancreatic secretion and immunoreactive secretin (IRS) release after intraduodenal instillation of bile in man | journal = Gut | volume = 19 | issue = 3 | pages = 180–184 | date = March 1978 | pmid = 631638 | pmc = 1411891 | doi = 10.1136/gut.19.3.180 }}</ref>


Secretin also increases water and bicarbonate secretion from duodenal [[Brunner's gland]]s to buffer the incoming [[protons]] of the acidic chyme,<ref name="isbn0-7216-0240-1">{{cite book |last1=Hall |first1=John E. |last2=Guyton |first2=Arthur C. |title=Textbook of medical physiology |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2006 |pages=800–1 |isbn=978-0-7216-0240-0 }}</ref> and also reduces acid secretion by [[parietal cells]] of the [[stomach]].<ref name="isbn0-7020-3085-6">{{cite book |editor1-last=Colledge |editor1-first=NR |editor2-last=Walker |editor2-first=BR |editor3-last=Ralston |editor3-first=SH |last1=Palmer |first1=KR |last2=Penman |first2=ID |title=Davidson's Principles and Practice of Medicine |edition= 20th |publisher=Churchill Livingstone |location=Edinburgh |year=2010 |isbn=978-0-7020-3085-7 |chapter=Alimentary track and pancreatic disease |page=844}}</ref> It does this through at least three mechanisms: 1) By stimulating release of [[somatostatin]], 2) By inhibiting release of [[gastrin]] in the [[pyloric antrum]], and 3) By direct [[downregulation]] of the parietal cell acid secretory mechanics.<ref name="isbn9781437717532">{{cite book |last1=Boron |first1=Walter F. |last2=Boulpaep |first2=Emile L. |title=Medical Physiology |edition= 2nd |publisher=Saunders |location=Philadelphia |year=2012 |page=1352 |isbn=978-1-4377-1753-2 |chapter=Acid secretion }}</ref><ref name="isbn0-07-022001-8"/>
Secretin also increases water and bicarbonate secretion from duodenal [[Brunner's gland]]s to buffer the incoming [[protons]] of the acidic chyme,<ref name="isbn0-7216-0240-1">{{cite book | vauthors = Hall JE, Guyton AC |title=Textbook of medical physiology |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2006 |pages=800–1 |isbn=978-0-7216-0240-0 }}</ref> and also reduces acid secretion by [[parietal cells]] of the [[stomach]].<ref name="isbn0-7020-3085-6">{{cite book | veditors = Colledge NR, Walker BR, Ralston SH | vauthors = Palmer KR, Penman ID |title=Davidson's Principles and Practice of Medicine |edition= 20th |publisher=Churchill Livingstone |location=Edinburgh |year=2010 |isbn=978-0-7020-3085-7 |chapter=Alimentary track and pancreatic disease |page=844}}</ref> It does this through at least three mechanisms: 1) By stimulating release of [[somatostatin]], 2) By inhibiting release of [[gastrin]] in the [[pyloric antrum]], and 3) By direct [[downregulation]] of the parietal cell acid secretory mechanics.<ref name="isbn9781437717532">{{cite book | vauthors = Boron WF, Boulpaep EL |title=Medical Physiology |edition= 2nd |publisher=Saunders |location=Philadelphia |year=2012 |page=1352 |isbn=978-1-4377-1753-2 |chapter=Acid secretion }}</ref><ref name="isbn0-07-022001-8"/>


It counteracts [[blood glucose]] concentration spikes by triggering increased [[insulin]] release from pancreas, following oral [[glucose]] intake.<ref name="pmid5415678">{{cite journal |vauthors=Kraegen EW, Chisholm DJ, Young JD, Lazarus L |title=The gastrointestinal stimulus to insulin release. II. A dual action of secretin |journal=The Journal of Clinical Investigation |volume=49 |issue=3 |pages=524–9 |year=1970 |pmid=5415678 |pmc=322500 |doi=10.1172/JCI106262 }}</ref>
It counteracts [[blood glucose]] concentration spikes by triggering increased [[insulin]] release from pancreas, following oral [[glucose]] intake.<ref name="pmid5415678">{{cite journal | vauthors = Kraegen EW, Chisholm DJ, Young JD, Lazarus L | title = The gastrointestinal stimulus to insulin release. II. A dual action of secretin | journal = The Journal of Clinical Investigation | volume = 49 | issue = 3 | pages = 524–529 | date = March 1970 | pmid = 5415678 | pmc = 322500 | doi = 10.1172/JCI106262 }}</ref>


====Osmoregulation====
====Osmoregulation====
Secretin modulates [[Osmoregulation|water]] and [[electrolyte]] transport in [[pancreatic duct]] cells,<ref name="pmid7875488">{{cite journal |vauthors=Villanger O, Veel T, Raeder MG |title=Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase |journal=Gastroenterology |volume=108 |issue=3 |pages=850–9 |year=1995 |pmid=7875488 |doi=10.1016/0016-5085(95)90460-3 }}</ref> liver [[cholangiocytes]],<ref name="pmid9148905">{{cite journal |vauthors=Marinelli RA, Pham L, Agre P, LaRusso NF |title=Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane. Evidence for a secretin-induced vesicular translocation of aquaporin-1 |journal=The Journal of Biological Chemistry |volume=272 |issue=20 |pages=12984–8 |year=1997 |pmid=9148905 |doi=10.1074/jbc.272.20.12984 |doi-access=free }}</ref> and [[epididymis]] epithelial cells.<ref name="pmid14749298">{{cite journal |vauthors=Chow BK, Cheung KH, Tsang EM, Leung MC, Lee SM, Wong PY |title=Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion |journal=Biology of Reproduction |volume=70 |issue=6 |pages=1594–9 |year=2004 |pmid=14749298 |doi=10.1095/biolreprod.103.024257 |doi-access=free }}</ref> It is found<ref name="pmid19318428">{{cite journal |vauthors=Cheng CY, Chu JY, Chow BK |title=Vasopressin-independent mechanisms in controlling water homeostasis |journal=Journal of Molecular Endocrinology |volume=43 |issue=3 |pages=81–92 |year=2009 |pmid=19318428 |doi=10.1677/JME-08-0123 |doi-access=free }}</ref> to play a role in the [[vasopressin]]-independent regulation of [[Renal physiology|renal water reabsorption]].<ref name="Chu07"/>
Secretin modulates [[Osmoregulation|water]] and [[electrolyte]] transport in [[pancreatic duct]] cells,<ref name="pmid7875488">{{cite journal | vauthors = Villanger O, Veel T, Raeder MG | title = Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase | journal = Gastroenterology | volume = 108 | issue = 3 | pages = 850–859 | date = March 1995 | pmid = 7875488 | doi = 10.1016/0016-5085(95)90460-3 | doi-access = free }}</ref> liver [[cholangiocytes]],<ref name="pmid9148905">{{cite journal | vauthors = Marinelli RA, Pham L, Agre P, LaRusso NF | title = Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane. Evidence for a secretin-induced vesicular translocation of aquaporin-1 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 20 | pages = 12984–12988 | date = May 1997 | pmid = 9148905 | doi = 10.1074/jbc.272.20.12984 | doi-access = free }}</ref> and [[epididymis]] epithelial cells.<ref name="pmid14749298">{{cite journal | vauthors = Chow BK, Cheung KH, Tsang EM, Leung MC, Lee SM, Wong PY | title = Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion | journal = Biology of Reproduction | volume = 70 | issue = 6 | pages = 1594–1599 | date = June 2004 | pmid = 14749298 | doi = 10.1095/biolreprod.103.024257 | s2cid = 1189550 | doi-access = }}</ref> It is found<ref name="pmid19318428">{{cite journal | vauthors = Cheng CY, Chu JY, Chow BK | title = Vasopressin-independent mechanisms in controlling water homeostasis | journal = Journal of Molecular Endocrinology | volume = 43 | issue = 3 | pages = 81–92 | date = September 2009 | pmid = 19318428 | doi = 10.1677/JME-08-0123 | doi-access = free }}</ref> to play a role in the [[vasopressin]]-independent regulation of [[Renal physiology|renal water reabsorption]].<ref name="Chu07"/>


Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the [[hypothalamus]] and along the neurohypophysial tract to [[neurohypophysis]]. During increased osmolality, it is released from the [[posterior pituitary]]. In the hypothalamus, it activates [[vasopressin]] release.<ref name="Chu"/> It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release.<ref name="pmid20739612">{{cite journal |vauthors=Lee VH, Lee LT, Chu JY, Lam IP, Siu FK, Vaudry H, Chow BK |title=An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II |journal=FASEB Journal |volume=24 |issue=12 |pages=5024–32 |year=2010 |pmid=20739612 |pmc=2992369 |doi=10.1096/fj.10-165399 }}</ref>
Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the [[hypothalamus]] and along the neurohypophysial tract to [[neurohypophysis]]. During increased osmolality, it is released from the [[posterior pituitary]]. In the hypothalamus, it activates [[vasopressin]] release.<ref name="Chu"/> It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release.<ref name="pmid20739612">{{cite journal | vauthors = Lee VH, Lee LT, Chu JY, Lam IP, Siu FK, Vaudry H, Chow BK | title = An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II | journal = FASEB Journal | volume = 24 | issue = 12 | pages = 5024–5032 | date = December 2010 | pmid = 20739612 | pmc = 2992369 | doi = 10.1096/fj.10-165399 | doi-access = free }}</ref>


It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D [[syndrome of inappropriate antidiuretic hormone hypersecretion]] (SIADH).<ref name="Chu"/> In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of [[aquaporin 2]], or both are found.<ref name="Chu"/> It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."<ref name="Chu"/>
It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D [[syndrome of inappropriate antidiuretic hormone hypersecretion]] (SIADH).<ref name="Chu"/> In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of [[aquaporin 2]], or both are found.<ref name="Chu"/> It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."<ref name="Chu"/>


====Food intake====
====Food intake====
Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the [[paraventricular nucleus]] and the [[arcuate nucleus]], which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating an anorectic role of the peptide. This function of the peptide is mediated by the [[central melanocortin system]].<ref name="pmid20927047">{{cite journal |vauthors=Cheng CY, Chu JY, Chow BK |title=Central and peripheral administration of secretin inhibits food intake in mice through the activation of the melanocortin system |journal=Neuropsychopharmacology |volume=36 |issue=2 |pages=459–71 |year=2011 |pmid=20927047 |pmc=3055665 |doi=10.1038/npp.2010.178 }}</ref>
Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the [[paraventricular nucleus]] and the [[arcuate nucleus]], which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating an anorectic role of the peptide. This function of the peptide is mediated by the [[central melanocortin system]].<ref name="pmid20927047">{{cite journal | vauthors = Cheng CY, Chu JY, Chow BK | title = Central and peripheral administration of secretin inhibits food intake in mice through the activation of the melanocortin system | journal = Neuropsychopharmacology | volume = 36 | issue = 2 | pages = 459–471 | date = January 2011 | pmid = 20927047 | pmc = 3055665 | doi = 10.1038/npp.2010.178 }}</ref>


== Uses ==
== Uses ==
Secretin is used in a diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with [[magnetic resonance imaging]], a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum.<ref>{{cite journal|last1=Lieb|first1=John-G|title=Pancreatic function testing: Here to stay for the 21st century|journal=World Journal of Gastroenterology|date=2008|volume=14|issue=20|pages=3149–58|doi=10.3748/WJG.14.3149|pmid=18506918|pmc=2712845}}</ref><ref>{{cite journal|last1=Domínguez Muñoz|first1=J. Enrique|title=Diagnosis of chronic pancreatitis: Functional testing|journal=Best Practice & Research Clinical Gastroenterology|date=June 2010|volume=24|issue=3|pages=233–241|doi=10.1016/j.bpg.2010.03.008|pmid=20510825}}</ref><ref name="urlMedlinePlus Medical Encyclopedia: Secretin stimulation test">{{cite encyclopedia |url=https://www.nlm.nih.gov/medlineplus/ency/article/003892.htm#Definition |title=Secretin stimulation test |encyclopedia=MedlinePlus Medical Encyclopedia |publisher=United States National Library of Medicine |access-date=2008-11-01 }}</ref>
Secretin is used in diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with [[magnetic resonance imaging]], a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum.<ref>{{cite journal | vauthors = Lieb JG, Draganov PV | title = Pancreatic function testing: here to stay for the 21st century | journal = World Journal of Gastroenterology | volume = 14 | issue = 20 | pages = 3149–3158 | date = May 2008 | pmid = 18506918 | pmc = 2712845 | doi = 10.3748/WJG.14.3149 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Domínguez Muñoz JE | title = Diagnosis of chronic pancreatitis: Functional testing | journal = Best Practice & Research. Clinical Gastroenterology | volume = 24 | issue = 3 | pages = 233–241 | date = June 2010 | pmid = 20510825 | doi = 10.1016/j.bpg.2010.03.008 }}</ref><ref name="urlMedlinePlus Medical Encyclopedia: Secretin stimulation test">{{cite encyclopedia |url=https://www.nlm.nih.gov/medlineplus/ency/article/003892.htm#Definition |title=Secretin stimulation test |encyclopedia=MedlinePlus Medical Encyclopedia |publisher=United States National Library of Medicine |access-date=2008-11-01 }}</ref>


A recombinant human secretin has been available since 2004 for these diagnostic purposes.<ref name="urlHuman Secretin">{{cite web |url=https://www.fda.gov/cder/consumerinfo/druginfo/Human_Secretin.HTM |title=Human Secretin |date=2004-07-13 |work=Patient Information Sheets |publisher=United States Food and Drug Administration |access-date=2008-11-01 |archive-url=https://web.archive.org/web/20090511200544/https://www.fda.gov/cder/consumerinfo/druginfo/Human_Secretin.HTM |archive-date=May 11, 2009 }}</ref> There were problems with the availability of this agent from 2012 to 2015.<ref>{{cite journal|last1=American Society of Health-System Pharmacists|title=Secretin Injection|journal=Current Drug Shortage Bulletin|date=5 August 2015|url=http://www.ashp.org/menu/DrugShortages/CurrentShortages/Bulletin.aspx?id=913}}</ref>
A recombinant human secretin has been available since 2004 for these diagnostic purposes.<ref name="urlHuman Secretin">{{cite web |url=https://www.fda.gov/cder/consumerinfo/druginfo/Human_Secretin.HTM |title=Human Secretin |date=2004-07-13 |work=Patient Information Sheets |publisher=United States Food and Drug Administration |access-date=2008-11-01 |archive-url=https://web.archive.org/web/20090511200544/https://www.fda.gov/cder/consumerinfo/druginfo/Human_Secretin.HTM |archive-date=May 11, 2009 }}</ref> There were problems with the availability of this agent from 2012 to 2015.<ref>{{cite journal|last1=American Society of Health-System Pharmacists|title=Secretin Injection|journal=Current Drug Shortage Bulletin|date=5 August 2015|url=http://www.ashp.org/menu/DrugShortages/CurrentShortages/Bulletin.aspx?id=913|access-date=9 November 2016|archive-date=9 November 2016|archive-url=https://web.archive.org/web/20161109221004/http://www.ashp.org/menu/DrugShortages/CurrentShortages/Bulletin.aspx?id=913|url-status=dead}}</ref>


==Research==
==Research==
A wave of enthusiasm for secretin as a possible treatment for [[autism spectrum|autism]] arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest.<ref>{{cite news|last1=Stokstad|first1=Erik|title=News this Week: Stalled Trial for Autism Highlights Dilemma of Alternative Treatments|url=http://science.sciencemag.org/content/321/5887/news-summaries|work=Science|date=18 July 2008|pages=324|language=en}}</ref><ref name="urlThe Use of Secretin to Treat Autism">{{cite web |url=http://www.nichd.nih.gov/news/releases/secretin.cfm |title=The Use of Secretin to Treat Autism |date=1998-10-16 |work=NIH News Alert |publisher=United States National Institutes of Health |access-date=2008-11-30 }}</ref><ref>{{cite journal |vauthors=Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW |title=Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder |journal=The New England Journal of Medicine |volume=341 |issue=24 |pages=1801–6 |year=1999 |pmid=10588965 |doi=10.1056/NEJM199912093412404 }}</ref>
A wave of enthusiasm for secretin as a possible treatment for [[autism spectrum|autism]] arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest.<ref>{{cite news| vauthors = Stokstad E |title=News this Week: Stalled Trial for Autism Highlights Dilemma of Alternative Treatments|url=http://science.sciencemag.org/content/321/5887/news-summaries|work=Science|date=18 July 2008|pages=324|language=en}}</ref><ref name="urlThe Use of Secretin to Treat Autism">{{cite web |url=http://www.nichd.nih.gov/news/releases/secretin.cfm |title=The Use of Secretin to Treat Autism |date=1998-10-16 |work=NIH News Alert |publisher=United States National Institutes of Health |access-date=2008-11-30 }}</ref><ref>{{cite journal | vauthors = Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW | title = Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder | journal = The New England Journal of Medicine | volume = 341 | issue = 24 | pages = 1801–1806 | date = December 1999 | pmid = 10588965 | doi = 10.1056/NEJM199912093412404 | doi-access = free }}</ref>


A high-affinity and optimized secretin receptor antagonist (Y10,c[E16,K20],I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.<ref>{{cite journal |vauthors=Dong M, Harikumar KG, Raval SR, Milburn JE, Clark C, Alcala-Torano R, Mobarec JC, Reynolds CA, Ghirlanda G, Christopoulos A, Wootten D, Sexton PM, Miller, LJ |title=Rational development of a high-affinity secretin receptor antagonist |journal=Biochemical Pharmacology |year=2020|volume=177 |page=113929 | doi=10.1016/j.bcp.2020.113929 |pmid=32217097 |pmc=7299832 }}</ref>
A high-affinity and optimized secretin receptor antagonist (Y10,c[E16,K20],I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.<ref>{{cite journal | vauthors = Dong M, Harikumar KG, Raval SR, Milburn JE, Clark C, Alcala-Torano R, Mobarec JC, Reynolds CA, Ghirlanda G, Christopoulos A, Wootten D, Sexton PM, Miller LJ | display-authors = 6 | title = Rational development of a high-affinity secretin receptor antagonist | journal = Biochemical Pharmacology | volume = 177 | pages = 113929 | date = July 2020 | pmid = 32217097 | pmc = 7299832 | doi = 10.1016/j.bcp.2020.113929 }}</ref>


==See also==
== See also ==
* [[Secretin family]]
* [[Secretin family]]
* [[Secretin receptor]]
* [[Secretin receptor]]


==References==
== References ==
{{Reflist|30em}}
{{Reflist|30em}}


==Further reading==
== Further reading ==
{{refbegin | colwidth=30em }}
{{refbegin | colwidth=30em }}
*{{cite journal |vauthors=Saus E, Brunet A, Armengol L, Alonso P, Crespo JM, Fernández-Aranda F, Guitart M, Martín-Santos R, Menchón JM, Navinés R, Soria V, Torrens M, Urretavizcaya M, Vallès V, Gratacòs M, Estivill X |title=Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients |journal=Journal of Psychiatric Research |volume=44 |issue=14 |pages=971–8 |year=2010 |pmid=20398908 |doi=10.1016/j.jpsychires.2010.03.007 |url=https://zenodo.org/record/3420197 }}
* {{cite journal | vauthors = Saus E, Brunet A, Armengol L, Alonso P, Crespo JM, Fernández-Aranda F, Guitart M, Martín-Santos R, Menchón JM, Navinés R, Soria V, Torrens M, Urretavizcaya M, Vallès V, Gratacòs M, Estivill X | display-authors = 6 | title = Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients | journal = Journal of Psychiatric Research | volume = 44 | issue = 14 | pages = 971–978 | date = October 2010 | pmid = 20398908 | doi = 10.1016/j.jpsychires.2010.03.007 }}{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}
*{{cite journal |vauthors=Bertenshaw GP, Turk BE, Hubbard SJ, Matters GL, Bylander JE, Crisman JM, Cantley LC, Bond JS |title=Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity |journal=The Journal of Biological Chemistry |volume=276 |issue=16 |pages=13248–55 |year=2001 |pmid=11278902 |doi=10.1074/jbc.M011414200 |doi-access=free }}
* {{cite journal | vauthors = Bertenshaw GP, Turk BE, Hubbard SJ, Matters GL, Bylander JE, Crisman JM, Cantley LC, Bond JS | display-authors = 6 | title = Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 13248–13255 | date = April 2001 | pmid = 11278902 | doi = 10.1074/jbc.M011414200 | doi-access = free }}
*{{cite journal |vauthors=Lee LT, Lam IP, Chow BK |title=A functional variable number of tandem repeats is located at the 5' flanking region of the human secretin gene plays a downregulatory role in expression |journal=Journal of Molecular Neuroscience |volume=36 |issue=1–3 |pages=125–31 |year=2008 |pmid=18566919 |doi=10.1007/s12031-008-9083-5 |s2cid=29982279 }}
* {{cite journal | vauthors = Lee LT, Lam IP, Chow BK | title = A functional variable number of tandem repeats is located at the 5' flanking region of the human secretin gene plays a downregulatory role in expression | journal = Journal of Molecular Neuroscience | volume = 36 | issue = 1–3 | pages = 125–131 | date = November 2008 | pmid = 18566919 | doi = 10.1007/s12031-008-9083-5 | s2cid = 29982279 }}
*{{cite journal |vauthors=Nussdorfer GG, Bahçelioglu M, Neri G, Malendowicz LK |title=Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis |journal=Peptides |volume=21 |issue=2 |pages=309–24 |year=2000 |pmid=10764961 |doi=10.1016/S0196-9781(99)00193-X |s2cid=42207065 }}
* {{cite journal | vauthors = Nussdorfer GG, Bahçelioglu M, Neri G, Malendowicz LK | title = Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis | journal = Peptides | volume = 21 | issue = 2 | pages = 309–324 | date = February 2000 | pmid = 10764961 | doi = 10.1016/S0196-9781(99)00193-X | s2cid = 42207065 }}
*{{cite journal |vauthors=Lossi L, Bottarelli L, Candusso ME, Leiter AB, Rindi G, Merighi A |title=Transient expression of secretin in serotoninergic neurons of mouse brain during development |journal=The European Journal of Neuroscience |volume=20 |issue=12 |pages=3259–69 |year=2004 |pmid=15610158 |doi=10.1111/j.1460-9568.2004.03816.x |s2cid=398304 }}
* {{cite journal | vauthors = Lossi L, Bottarelli L, Candusso ME, Leiter AB, Rindi G, Merighi A | title = Transient expression of secretin in serotoninergic neurons of mouse brain during development | journal = The European Journal of Neuroscience | volume = 20 | issue = 12 | pages = 3259–3269 | date = December 2004 | pmid = 15610158 | doi = 10.1111/j.1460-9568.2004.03816.x | s2cid = 398304 }}
*{{cite journal |vauthors=Lee SM, Yung WH, Chen L, Chow BK |title=Expression and spatial distribution of secretin and secretin receptor in human cerebellum |journal=NeuroReport |volume=16 |issue=3 |pages=219–22 |year=2005 |pmid=15706223 |doi=10.1097/00001756-200502280-00003|s2cid=10500720 }}
* {{cite journal | vauthors = Lee SM, Yung WH, Chen L, Chow BK | title = Expression and spatial distribution of secretin and secretin receptor in human cerebellum | journal = NeuroReport | volume = 16 | issue = 3 | pages = 219–222 | date = February 2005 | pmid = 15706223 | doi = 10.1097/00001756-200502280-00003 | s2cid = 10500720 }}
*{{cite journal |vauthors=Lam IP, Lee LT, Choi HS, Alpini G, Chow BK |title=Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP) |journal=American Journal of Physiology. Gastrointestinal and Liver Physiology |volume=297 |issue=1 |pages=G90–7 |year=2009 |pmid=19372104 |pmc=2711755 |doi=10.1152/ajpgi.00094.2009 }}
* {{cite journal | vauthors = Lam IP, Lee LT, Choi HS, Alpini G, Chow BK | title = Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP) | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 297 | issue = 1 | pages = G90–G97 | date = July 2009 | pmid = 19372104 | pmc = 2711755 | doi = 10.1152/ajpgi.00094.2009 }}
*{{cite journal |vauthors=Yamagata T, Aradhya S, Mori M, Inoue K, Momoi MY, Nelson DL |title=The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism |journal=Genomics |volume=80 |issue=2 |pages=185–94 |year=2002 |pmid=12160732 |doi=10.1006/geno.2002.6814 }}
* {{cite journal | vauthors = Yamagata T, Aradhya S, Mori M, Inoue K, Momoi MY, Nelson DL | title = The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism | journal = Genomics | volume = 80 | issue = 2 | pages = 185–194 | date = August 2002 | pmid = 12160732 | doi = 10.1006/geno.2002.6814 }}
*{{cite journal |vauthors=Lee LT, Tan-Un KC, Chow BK |title=Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by cyclin-dependent kinase 1 |journal=Annals of the New York Academy of Sciences |volume=1070 |issue= 1|pages=393–8 |year=2006 |pmid=16888198 |doi=10.1196/annals.1317.051 |bibcode=2006NYASA1070..393L |s2cid=36959997 }}
* {{cite journal | vauthors = Lee LT, Tan-Un KC, Chow BK | title = Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by cyclin-dependent kinase 1 | journal = Annals of the New York Academy of Sciences | volume = 1070 | issue = 1 | pages = 393–398 | date = July 2006 | pmid = 16888198 | doi = 10.1196/annals.1317.051 | s2cid = 36959997 | bibcode = 2006NYASA1070..393L }}
*{{cite journal |vauthors=Onori P, Wise C, Gaudio E, Franchitto A, Francis H, Carpino G, Lee V, Lam I, Miller T, Dostal DE, Glaser SS |title=Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor |journal=International Journal of Cancer |volume=127 |issue=1 |pages=43–54 |year=2010 |pmid=19904746 |doi=10.1002/ijc.25028 |s2cid=2789418 |doi-access=free }}
* {{cite journal | vauthors = Onori P, Wise C, Gaudio E, Franchitto A, Francis H, Carpino G, Lee V, Lam I, Miller T, Dostal DE, Glaser SS | display-authors = 6 | title = Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor | journal = International Journal of Cancer | volume = 127 | issue = 1 | pages = 43–54 | date = July 2010 | pmid = 19904746 | doi = 10.1002/ijc.25028 | s2cid = 2789418 | doi-access = free }}
*{{cite journal |vauthors=Lee LT, Tan-Un KC, Pang RT, Lam DT, Chow BK |title=Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element |journal=Molecular Endocrinology |volume=18 |issue=7 |pages=1740–55 |year=2004 |pmid=15118068 |doi=10.1210/me.2003-0461 |doi-access=free }}
* {{cite journal | vauthors = Lee LT, Tan-Un KC, Pang RT, Lam DT, Chow BK | title = Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element | journal = Molecular Endocrinology | volume = 18 | issue = 7 | pages = 1740–1755 | date = July 2004 | pmid = 15118068 | doi = 10.1210/me.2003-0461 | doi-access = free }}
*{{cite journal |vauthors=Lu Y, Owyang C |title=Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways |journal=Neurogastroenterology and Motility |volume=21 |issue=7 |pages=754–e47 |year=2009 |pmid=19239625 |pmc=2743409 |doi=10.1111/j.1365-2982.2009.01271.x }}
* {{cite journal | vauthors = Lu Y, Owyang C | title = Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways | journal = Neurogastroenterology and Motility | volume = 21 | issue = 7 | pages = 754–e47 | date = July 2009 | pmid = 19239625 | pmc = 2743409 | doi = 10.1111/j.1365-2982.2009.01271.x }}
*{{cite journal |vauthors=Gandhi S, Rubinstein I, Tsueshita T, Onyuksel H |title=Secretin self-assembles and interacts spontaneously with phospholipids in vitro |journal=Peptides |volume=23 |issue=1 |pages=201–4 |year=2002 |pmid=11814635 |doi=10.1016/S0196-9781(01)00596-4 |s2cid=19705403 }}
* {{cite journal | vauthors = Gandhi S, Rubinstein I, Tsueshita T, Onyuksel H | title = Secretin self-assembles and interacts spontaneously with phospholipids in vitro | journal = Peptides | volume = 23 | issue = 1 | pages = 201–204 | date = January 2002 | pmid = 11814635 | doi = 10.1016/S0196-9781(01)00596-4 | s2cid = 19705403 }}
*{{cite journal |vauthors=Lam IP, Lee LT, Choi HS, Chow BK |title=Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells |journal=Annals of the New York Academy of Sciences |volume=1070 |issue= 1|pages=371–5 |year=2006 |pmid=16888194 |doi=10.1196/annals.1317.047 |bibcode=2006NYASA1070..371L |s2cid=37244976 }}
* {{cite journal | vauthors = Lam IP, Lee LT, Choi HS, Chow BK | title = Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells | journal = Annals of the New York Academy of Sciences | volume = 1070 | issue = 1 | pages = 371–375 | date = July 2006 | pmid = 16888194 | doi = 10.1196/annals.1317.047 | s2cid = 37244976 | bibcode = 2006NYASA1070..371L }}
*{{cite journal |vauthors=Luttrell LM |title=Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors |journal=Molecular Biotechnology |volume=39 |issue=3 |pages=239–64 |year=2008 |pmid=18240029 |doi=10.1007/s12033-008-9031-1 |s2cid=45173229 }}
* {{cite journal | vauthors = Luttrell LM | title = Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors | journal = Molecular Biotechnology | volume = 39 | issue = 3 | pages = 239–264 | date = July 2008 | pmid = 18240029 | doi = 10.1007/s12033-008-9031-1 | s2cid = 45173229 }}
*{{cite journal |vauthors=Du K, Couvineau A, Rouyer-Fessard C, Nicole P, Laburthe M |title=Human VPAC1 receptor selectivity filter. Identification of a critical domain for restricting secretin binding |journal=The Journal of Biological Chemistry |volume=277 |issue=40 |pages=37016–22 |year=2002 |pmid=12133828 |doi=10.1074/jbc.M203049200 |doi-access=free }}
* {{cite journal | vauthors = Du K, Couvineau A, Rouyer-Fessard C, Nicole P, Laburthe M | title = Human VPAC1 receptor selectivity filter. Identification of a critical domain for restricting secretin binding | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 37016–37022 | date = October 2002 | pmid = 12133828 | doi = 10.1074/jbc.M203049200 | doi-access = free }}
*{{cite journal |vauthors=Portela-Gomes GM, Johansson H, Olding L, Grimelius L |title=Co-localization of neuroendocrine hormones in the human fetal pancreas |journal=European Journal of Endocrinology |volume=141 |issue=5 |pages=526–33 |year=1999 |pmid=10576771 |doi=10.1530/eje.0.1410526 |doi-access=free }}
* {{cite journal | vauthors = Portela-Gomes GM, Johansson H, Olding L, Grimelius L | title = Co-localization of neuroendocrine hormones in the human fetal pancreas | journal = European Journal of Endocrinology | volume = 141 | issue = 5 | pages = 526–533 | date = November 1999 | pmid = 10576771 | doi = 10.1530/eje.0.1410526 | doi-access = free }}
*{{cite journal |vauthors=Mutoh H, Ratineau C, Ray S, Leiter AB |title=Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells |journal=Alimentary Pharmacology & Therapeutics |volume=14 |issue=Suppl 1 |pages=170–5 |year=2000 |pmid=10807420 |doi=10.1046/j.1365-2036.2000.014s1170.x |s2cid=25989697 |doi-access=free }}
* {{cite journal | vauthors = Mutoh H, Ratineau C, Ray S, Leiter AB | title = Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells | journal = Alimentary Pharmacology & Therapeutics | volume = 14 | issue = Suppl 1 | pages = 170–175 | date = April 2000 | pmid = 10807420 | doi = 10.1046/j.1365-2036.2000.014s1170.x | s2cid = 25989697 | doi-access = }}
{{refend}}
{{refend}}


==External links==
== External links ==
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/secretin.html Overview at colostate.edu]
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/secretin.html Overview at colostate.edu]
* {{MeshName|Secretin}}
* {{MeshName|Secretin}}
* {{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 6/6ch2/s6ch2_17 |chapter-url=http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_17.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_17.htm|archive-date=2016-03-24}}
* {{cite book| title= Essentials of Human Physiology| vauthors = Nosek TM | chapter=Section 6/6ch2/s6ch2_17 |chapter-url=http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_17.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section6/6ch2/s6ch2_17.htm|archive-date=2016-03-24}}


{{Gastrointestinal physiology}}
{{Gastrointestinal physiology}}

Latest revision as of 20:35, 14 August 2024

SCT
Identifiers
AliasesSCT, entrez:6343, secretin
External IDsOMIM: 182099; MGI: 99466; HomoloGene: 137358; GeneCards: SCT; OMA:SCT - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6343

20287

Ensembl

ENSG00000070031
ENSG00000274473

ENSMUSG00000038580

UniProt

P09683

Q08535

RefSeq (mRNA)

NM_021920

NM_011328
NM_001287171
NM_001309439

RefSeq (protein)

NP_068739

NP_001274100
NP_001296368
NP_035458

Location (UCSC)Chr 11: 0.63 – 0.63 MbChr 7: 140.86 – 140.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands.[5] In humans, the secretin peptide is encoded by the SCT gene.[6]

Secretin helps regulate the pH of the duodenum by inhibiting the secretion of gastric acid from the parietal cells of the stomach and stimulating the production of bicarbonate from the ductal cells of the pancreas.[7][8] It also stimulates the secretion of bicarbonate and water by cholangiocytes in the bile duct, protecting it from bile acids by controlling the pH and promoting the flow in the duct.[9] Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, cholecystokinin (CCK), stimulates the gallbladder to contract, delivering its stored bile.

Prosecretin is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by gastric acid. This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid.[10]

In 2007, secretin was discovered to play a role in osmoregulation by acting on the hypothalamus, pituitary gland, and kidney.[11][12]

History

[edit]

In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion.[13] It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion secretin. This type of 'chemical messenger' substance is now called a hormone, a term coined by Starling in 1905.[14]

Secretin is frequently erroneously stated to have been the first hormone identified.[15] However, British researchers George Oliver and Edward Albert Schäfer had already published their findings of an adrenal extract increasing blood pressure and heart rate in brief reports in 1894 and a full publication in 1895, making adrenaline the first discovered hormone.[16][17]

Structure

[edit]

Secretin is initially synthesized as a 120 amino acid precursor protein known as prosecretin. This precursor contains an N-terminal signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid C-terminal peptide.[6]

The mature secretin peptide is a linear peptide hormone, which is composed of 27 amino acids and has a molecular weight of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of glucagon, vasoactive intestinal peptide (VIP), and gastric inhibitory peptide (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP.[18]

Secretin also has an amidated carboxyl-terminal amino acid which is valine.[19] The sequence of amino acids in secretin is H–His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val–NH2.[19]

Physiology

[edit]

Production and secretion

[edit]

Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the mucosa of the duodenum, and in smaller numbers in the jejunum of the small intestine.[20]

Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species; the acidity is due to hydrochloric acid in the chyme that enters the duodenum from the stomach via the pyloric sphincter.[21] Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.[22]

Secretin release is inhibited by H2 antagonists, which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released.[23]

Function

[edit]

pH regulation

[edit]

Secretin primarily functions to neutralize the pH in the duodenum, allowing digestive enzymes from the pancreas (e.g., pancreatic amylase and pancreatic lipase) to function optimally.[24]

Secretin targets the pancreas; pancreatic centroacinar cells have secretin receptors in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts ATP to cyclic AMP.[25] Cyclic AMP acts as second messenger in intracellular signal transduction and causes the organ to secrete a bicarbonate-rich fluid that flows into the intestine. Bicarbonate is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine.[26]

Secretin also increases water and bicarbonate secretion from duodenal Brunner's glands to buffer the incoming protons of the acidic chyme,[24] and also reduces acid secretion by parietal cells of the stomach.[27] It does this through at least three mechanisms: 1) By stimulating release of somatostatin, 2) By inhibiting release of gastrin in the pyloric antrum, and 3) By direct downregulation of the parietal cell acid secretory mechanics.[28][21]

It counteracts blood glucose concentration spikes by triggering increased insulin release from pancreas, following oral glucose intake.[29]

Osmoregulation

[edit]

Secretin modulates water and electrolyte transport in pancreatic duct cells,[30] liver cholangiocytes,[31] and epididymis epithelial cells.[32] It is found[33] to play a role in the vasopressin-independent regulation of renal water reabsorption.[11]

Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus and along the neurohypophysial tract to neurohypophysis. During increased osmolality, it is released from the posterior pituitary. In the hypothalamus, it activates vasopressin release.[12] It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release.[34]

It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).[12] In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found.[12] It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."[12]

Food intake

[edit]

Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the paraventricular nucleus and the arcuate nucleus, which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating an anorectic role of the peptide. This function of the peptide is mediated by the central melanocortin system.[35]

Uses

[edit]

Secretin is used in diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with magnetic resonance imaging, a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum.[36][37][38]

A recombinant human secretin has been available since 2004 for these diagnostic purposes.[39] There were problems with the availability of this agent from 2012 to 2015.[40]

Research

[edit]

A wave of enthusiasm for secretin as a possible treatment for autism arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest.[41][42][43]

A high-affinity and optimized secretin receptor antagonist (Y10,c[E16,K20],I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.[44]

See also

[edit]

References

[edit]
  1. ^ a b c ENSG00000274473 GRCh38: Ensembl release 89: ENSG00000070031, ENSG00000274473 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038580 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Häcki WH (September 1980). "Secretin". Clinics in Gastroenterology. 9 (3): 609–632. doi:10.1016/S0300-5089(21)00474-0. PMID 7000396.
  6. ^ a b Kopin AS, Wheeler MB, Leiter AB (March 1990). "Secretin: structure of the precursor and tissue distribution of the mRNA". Proceedings of the National Academy of Sciences of the United States of America. 87 (6): 2299–2303. Bibcode:1990PNAS...87.2299K. doi:10.1073/pnas.87.6.2299. JSTOR 2354038. PMC 53674. PMID 2315322.
  7. ^ Whitmore TE, Holloway JL, Lofton-Day CE, Maurer MF, Chen L, Quinton TJ, et al. (2000). "Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA". Cytogenetics and Cell Genetics. 90 (1–2): 47–52. doi:10.1159/000015658. PMID 11060443. S2CID 12850155.
  8. ^ Costanzo, Linda S. (2006). Physiology (3rd ed.). Philadelphia, PA: Saunders Elsevier. ISBN 9781416023203. OCLC 62326921.
  9. ^ Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ (May 2019). "Cholangiocyte pathobiology". Nature Reviews. Gastroenterology & Hepatology. 16 (5): 269–281. doi:10.1038/s41575-019-0125-y. PMC 6563606. PMID 30850822.
  10. ^ Gafvelin G, Jörnvall H, Mutt V (September 1990). "Processing of prosecretin: isolation of a secretin precursor from porcine intestine". Proceedings of the National Academy of Sciences of the United States of America. 87 (17): 6781–6785. Bibcode:1990PNAS...87.6781G. doi:10.1073/pnas.87.17.6781. PMC 54621. PMID 2395872.
  11. ^ a b Chu JY, Chung SC, Lam AK, Tam S, Chung SK, Chow BK (April 2007). "Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption". Molecular and Cellular Biology. 27 (7): 2499–2511. doi:10.1128/MCB.01088-06. PMC 1899889. PMID 17283064.
  12. ^ a b c d e Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK (September 2009). "Secretin as a neurohypophysial factor regulating body water homeostasis". Proceedings of the National Academy of Sciences of the United States of America. 106 (37): 15961–15966. Bibcode:2009PNAS..10615961C. doi:10.1073/pnas.0903695106. JSTOR 40484830. PMC 2747226. PMID 19805236.
  13. ^ Bayliss WM, Starling EH (September 1902). "The mechanism of pancreatic secretion". The Journal of Physiology. 28 (5): 325–353. doi:10.1113/jphysiol.1902.sp000920. PMC 1540572. PMID 16992627.
  14. ^ Hirst BH (October 2004). "Secretin and the exposition of hormonal control". The Journal of Physiology. 560 (Pt 2): 339. doi:10.1113/jphysiol.2004.073056. PMC 1665254. PMID 15308687.
  15. ^ Henriksen JH, Schaffalitzky de Muckadell OB (January 2002). "[Secretin--the first hormone]" [Secretin--the first hormone]. Ugeskrift for Laeger (in Danish). 164 (3): 320–325. PMID 11816326. INIST 13419424.
  16. ^ Oliver G, Schäfer EA (July 1895). "The Physiological Effects of Extracts of the Suprarenal Capsules". The Journal of Physiology. 18 (3): 230–276. doi:10.1113/jphysiol.1895.sp000564. PMC 1514629. PMID 16992252.
  17. ^ Oliver G, Schäfer EA (July 1895). "The Physiological Effects of Extracts of the Suprarenal Capsules". The Journal of Physiology. 18 (3): 230–276. doi:10.1113/jphysiol.1895.sp000564. PMC 1514629. PMID 16992252.
  18. ^ Williams RL (1981). Textbook of Endocrinology. Philadelphia: Saunders. p. 697. ISBN 978-0-7216-9398-9.
  19. ^ a b DeGroot LJ (1989). McGuigan JE (ed.). Endocrinology. Philadelphia: Saunders. pp. 2748. ISBN 978-0-7216-2888-2.
  20. ^ Polak JM, Coulling I, Bloom S, Pearse AG (1971). "Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa". Scandinavian Journal of Gastroenterology. 6 (8): 739–744. doi:10.3109/00365527109179946. PMID 4945081.
  21. ^ a b Frohman LA, Felig P (2001). "Gastrointestinal Hormones and Carcinoid Syndrome". In Ghosh PK, O'Dorisio TM (eds.). Endocrinology & metabolism. New York: McGraw-Hill, Medical Pub. Div. pp. 1675–701. ISBN 978-0-07-022001-0.
  22. ^ Ganong WF (2003). "Regulation of Gastrointestinal Function". Review of Medical Physiology (21st ed.). New York: McGraw-Hill, Medical Pub. Div. ISBN 978-0-07-140236-1.[page needed]
  23. ^ Rominger JM, Chey WY, Chang TM (July 1981). "Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases". Digestive Diseases and Sciences. 26 (7): 591–597. doi:10.1007/BF01367670. PMID 7249893. S2CID 7039025.
  24. ^ a b Hall JE, Guyton AC (2006). Textbook of medical physiology. St. Louis, Mo: Elsevier Saunders. pp. 800–1. ISBN 978-0-7216-0240-0.
  25. ^ Gardner JD (1978). "Receptors and gastrointestinal hormones". In Sleisenger MH, Fordtran JS (eds.). Gastrointestinal Disease (2nd ed.). Philadelphia: WB Saunders Company. pp. 179–95.
  26. ^ Osnes M, Hanssen LE, Flaten O, Myren J (March 1978). "Exocrine pancreatic secretion and immunoreactive secretin (IRS) release after intraduodenal instillation of bile in man". Gut. 19 (3): 180–184. doi:10.1136/gut.19.3.180. PMC 1411891. PMID 631638.
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Further reading

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