Proton-sensing G protein-coupled receptors

Last updated
Production of cAMP in response to activation of TDAG8 G protein-coupled receptor by low pH. Data from Wang et al., "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor". PHcAMP.png
Production of cAMP in response to activation of TDAG8 G protein-coupled receptor by low pH. Data from Wang et al., "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor".

Proton-sensing G protein-coupled receptors are transmembrane receptors which sense acidic pH and include GPR132 (G2A), GPR4, GPR68 (OGR1) and GPR65 (TDAG8). [2] These G protein-coupled receptors are activated when extracellular pH falls into the range of 6.4-6.8 (typical values are above 7.0). The functional role of the low pH sensitivity of the proton-sensing G protein-coupled receptors is being studied in several tissues where cells respond to conditions of low pH including bone and inflamed tissues. The four known proton-sensing G protein-coupled receptors are Class A receptors in subfamily A15.

Contents

Nociception

Pain sensation can be initiated by nociceptor cells that are sensory neurons with cell bodies located in the dorsal root ganglia. Some nociceptors respond to low pH and the pH-sensitive amiloride-sensitive cation channel 3 has been described as a modulator of acid-induced pain sensation. [3] However, results with amiloride-sensitive cation channel 3 gene knockout mice suggest that those channels do not fully account for acid-induced pain sensation. [4] Proton-sensing G protein-coupled receptors have been shown to be expressed in small-diameter neurons responsible for nociception where they may play a role in acid-induced pain sensation. [5] Acid-sensing neuron-mediated immediate pungent pain has been associated with acid-sensing ion channels. [6]

Other functions

Mice lacking the Ovarian cancer G protein-coupled receptor 1 gene (OGR1) had slower melanoma growth (KO) than control mice with OGR1 (FL), possibly due to a difference in macrophage activity. GPR68KO.PNG
Mice lacking the Ovarian cancer G protein-coupled receptor 1 gene (OGR1) had slower melanoma growth (KO) than control mice with OGR1 (FL), possibly due to a difference in macrophage activity.

Mice lacking each of the four identified proton-sensing GPCRs have been studied. [7] Results so far suggest that these GPCRs might regulate cell proliferation (immune system cells such as lymphocytes and macrophages), but due to redundancy and expression of multiple proton-sensing GPCRs family members in the same cell, multiple gene knockouts are needed. Results for mice lacking OGR1 suggested a possible role for proton-sensing GPCRs in osteoclasts.

Related Research Articles

<span class="mw-page-title-main">Nociceptor</span> Sensory neuron that detects pain

A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception.

<span class="mw-page-title-main">Melittin</span> Chemical compound

Melittin is the main component and the major pain-producing substance of honeybee venom. Melittin is a basic peptide consisting of 26 amino acids.

<span class="mw-page-title-main">Dorsal root ganglion</span> Cluster of neurons in a dorsal root of a spinal nerve

A dorsal root ganglion is a cluster of neurons in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dorsal root ganglia.

<span class="mw-page-title-main">G protein-gated ion channel</span>

G protein-gated ion channels are a family of transmembrane ion channels in neurons and atrial myocytes that are directly gated by G proteins.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">TRPM3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

<span class="mw-page-title-main">GPR4</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor 4 is a protein that in humans is encoded by the GPR4 gene.

<span class="mw-page-title-main">GPR68</span> Protein-coding gene in the species Homo sapiens

Ovarian cancer G-protein coupled receptor 1 is a protein that in humans is encoded by the GPR68 gene.

<span class="mw-page-title-main">GPR65</span>

Psychosine receptor is a G protein-coupled receptor (GPCR) protein that in humans is encoded by the GPR65 gene. GPR65 is also referred to as TDAG8.

<span class="mw-page-title-main">GPR132</span> Protein-coding gene in the species Homo sapiens

G protein coupled receptor 132, also termed G2A, is classified as a member of the proton sensing G protein coupled receptor (GPR) subfamily. Like other members of this subfamily, i.e. GPR4, GPR68 (OGR1), and GPR65 (TDAG8), G2A is a G protein coupled receptor that resides in the cell surface membrane, senses changes in extracellular pH, and can alter cellular function as a consequence of these changes. Subsequently, G2A was suggested to be a receptor for lysophosphatidylcholine (LPC). However, the roles of G2A as a pH-sensor or LPC receptor are disputed. Rather, current studies suggest that it is a receptor for certain metabolites of the polyunsaturated fatty acid, linoleic acid.

<span class="mw-page-title-main">GPR84</span>

Probable G-protein coupled receptor 84 is a protein that in humans is encoded by the GPR84 gene.

<span class="mw-page-title-main">Hydroxycarboxylic acid receptor 2</span> Protein-coding gene in the species Homo sapiens

Hydroxycarboxylic acid receptor 2 (HCA2), also known as niacin receptor 1 (NIACR1) and GPR109A, is a protein which in humans is encoded by the HCAR2 gene. HCA2, like the other hydroxycarboxylic acid receptors HCA1 and HCA3, is a Gi/o-coupled G protein-coupled receptor (GPCR). The primary endogenous agonists of HCA2 are D-β-hydroxybutyric acid and butyric acid (and their conjugate bases, β-hydroxybutyrate and butyrate). HCA2 is also a high-affinity biomolecular target for niacin (aka nicotinic acid).

<span class="mw-page-title-main">GPR56</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor 56 also known as TM7XN1 is a protein encoded by the ADGRG1 gene. GPR56 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

<span class="mw-page-title-main">GPR3</span> Protein

G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.

<span class="mw-page-title-main">ASIC1</span> Protein-coding gene in the species Homo sapiens

Acid-sensing ion channel 1 (ASIC1) also known as amiloride-sensitive cation channel 2, neuronal (ACCN2) or brain sodium channel 2 (BNaC2) is a protein that in humans is encoded by the ASIC1 gene. The ASIC1 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals. The cDNA of this gene was first cloned in 1996. The ASIC genes have splicing variants that encode different proteins that are called isoforms.

<span class="mw-page-title-main">ASIC3</span> Protein-coding gene in the species Homo sapiens

Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1) is a protein that in humans is encoded by the ASIC3 gene. The ASIC3 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals. The cDNA of this gene was first cloned in 1998. The ASIC genes have splicing variants that encode different proteins that are called isoforms.

<span class="mw-page-title-main">ASIC2</span> Protein-coding gene in the species Homo sapiens

Acid-sensing ion channel 2 (ASIC2) also known as amiloride-sensitive cation channel 1, neuronal (ACCN1) or brain sodium channel 1 (BNaC1) is a protein that in humans is encoded by the ASIC2 gene. The ASIC2 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals. The cDNA of this gene was first cloned in 1996. The ASIC genes have splicing variants that encode different proteins that are called isoforms.

<span class="mw-page-title-main">Taste</span> Sense of chemicals on the tongue

The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor cells located on taste buds in the oral cavity, mostly on the tongue. Taste, along with olfaction and trigeminal nerve stimulation, determines flavors of food and other substances. Humans have taste receptors on taste buds and other areas, including the upper surface of the tongue and the epiglottis. The gustatory cortex is responsible for the perception of taste.

<span class="mw-page-title-main">Psalmotoxin</span>

Psalmotoxin (PcTx1) is a spider toxin from the venom of the Trinidad tarantula Psalmopoeus cambridgei. It selectively blocks Acid Sensing Ion Channel 1-a (ASIC1a), which is a proton-gated sodium channel.

<span class="mw-page-title-main">Acid-sensing ion channel</span> Class of transport proteins

Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels activated by extracellular protons permeable to Na+. ASIC1 also shows low Ca2+ permeability. ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. These genes have splice variants that encode for several isoforms that are marked by a suffix. In mammals, acid-sensing ion channels (ASIC) are encoded by five genes that produce ASIC protein subunits: ASIC1, ASIC2, ASIC3, ASIC4, and ASIC5. Three of these protein subunits assemble to form the ASIC, which can combine into both homotrimeric and heterotrimeric channels typically found in both the central nervous system and peripheral nervous system. However, the most common ASICs are ASIC1a and ASIC1a/2a and ASIC3. ASIC2b is non-functional on its own but modulates channel activity when participating in heteromultimers and ASIC4 has no known function. On a broad scale, ASICs are potential drug targets due to their involvement in pathological states such as retinal damage, seizures, and ischemic brain injury.

References

  1. ↑ Wang JQ, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F (2004). "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor". J Biol Chem. 279 (44): 45626–45633. doi: 10.1074/jbc.M406966200 . PMID   15326175.
  2. ↑ Seuwen K, Ludwig MG, Wolf RM (2006). "Receptors for protons or lipid messengers or both?". J. Recept. Signal Transduct. Res. 26 (5–6): 599–610. doi:10.1080/10799890600932220. PMID   17118800. S2CID   2730341.
  3. ↑ Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A (2002). "A role for ASIC3 in the modulation of high-intensity pain stimuli". Proc Natl Acad Sci U S A. 99 (13): 8992–7. Bibcode:2002PNAS...99.8992C. doi: 10.1073/pnas.122245999 . PMC   124411 . PMID   12060708.
  4. ↑ Yen YT, Tu PH, Chen CJ, Lin YW, Hsieh ST, Chen CC (2009). "Role of acid-sensing ion channel 3 in sub-acute-phase inflammation". Molecular Pain . 5 (1): 1. doi:10.1186/1744-8069-5-1. PMC   2632618 . PMID   19126241.
  5. ↑ Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH (2007). "Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors" (PDF). Mol. Cell. Neurosci. 36 (2): 195–210. doi:10.1016/j.mcn.2007.06.010. PMID   17720533. S2CID   38351962.
  6. ↑ Bessac, B. F.; Jordt, S. -E. (2010). "Sensory Detection and Responses to Toxic Gases: Mechanisms, Health Effects, and Countermeasures". Proceedings of the American Thoracic Society. 7 (4): 269–277. doi:10.1513/pats.201001-004SM. PMC   3136963 . PMID   20601631.
  7. 1 2 Li H, Wang D, Singh LS, Berk M, Tan H, Zhao Z, Steinmetz R, Kirmani K, Wei G, Xu Y (2009). Aziz SA (ed.). "Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1". PLOS ONE. 4 (5): e5705. Bibcode:2009PLoSO...4.5705L. doi: 10.1371/journal.pone.0005705 . PMC   2684630 . PMID   19479052.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.