Alpha-7 nicotinic receptor
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The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits.[1] As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].
It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields post- and presynaptic excitation,[1] mainly by increased Ca2+ permeability.
Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina.[2] Functional α7 receptors are present in the submucous plexus neurons of the guinea-pig ileum.[3]
Medical relevance
[edit]Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and Alzheimer's disease.[4][5][6]
An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.[7]
Activation of α7 nicotinic acetylcholine receptor on mast cells, is a mechanism by which nicotine enhances atherosclerosis.[8]
Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.[9]
α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.[10] α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects.[11][12][13]
Ligands
[edit]Agonists
[edit]- (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan- 2-carboxamide: potent and highly subtype-selective[14]
- Tilorone.
- A-582941: partial agonist; activates ERK1/2 and CREB phosphorylation; enhances cognitive performance[15]
- AR-R17779: full agonist, nootropic
- Amyloid beta: neurotoxic marker of Alzheimer's disease[16]
- TC-1698: subtype-selective; neuroprotective effects via activation of the JAK2/PI-3K cascade, neutralized by angiotensin II AT(2) receptor activation[17]
- Bradanicline - partial agonist, in development for treatment of schizophrenia
- Encenicline - partial agonist with nootropic properties, in development for treatment of schizophrenia and Alzheimer's disease [18][19]
- GTS-21 - partial agonist, in development for treatment of schizophrenia and/or Alzheimer's disease
- PHA-543,613 - selective and potent agonist with nootropic properties [20][21]
- PNU-282,987 - selective and potent agonist, but may cause long QT syndrome
- PHA-709829: potent and subtype-selective; robust in vivo efficacy in a rat auditory sensory gating model[22]
- SSR-180,711: partial agonist[24]
- Tropisetron: subtype-selective partial agonist; 5-HT3 receptor antagonist[25]
- WAY-317,538 - selective potent full agonist with nootropic and neuroprotective properties
- Anabasine
- Acetylcholine
- Nicotine
- Epiboxidine[26]
- Choline[27]
- ICH-3: subtype-selective partial agonist[28]
Positive allosteric modulators (PAMs)
[edit]At least two types of positive allosteric modulators (PAMs) can be distinguished.[29]
- PNU-120,596[30]
- NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[31]
- AVL-3288: unlike the above PAMs, AVL-3288 does not affect α7 desensitization kinetics, and is readily brain penetrant. Improves cognitive behavior in animal models[32] In clinical development for cognitive deficits in schizophrenia.
- A-867744[33][34]
- Ivermectin
Other
[edit]Antagonists
[edit]It is found that anandamide and ethanol cause an additive inhibition on the function of α7-receptor by interacting with distinct regions of the receptor. Although ethanol inhibition of the α7-receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide is located in the transmembrane and carboxyl-terminal domains of the receptors.[38]
- Anandamide
- α-Bungarotoxin
- α-Conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible[39]
- β-Caryophyllene[40]
- Bupropion (very weakly)
- Dehydronorketamine
- Ethanol
- Hydroxybupropion (very weakly)
- Hydroxynorketamine
- Ketamine
- Kynurenic acid
- Memantine
- Lobeline
- Methyllycaconitine[20]
- Norketamine
- Quinolizidine (−)-1-epi-207I: α7 subtype preferring blocker[41]
See also
[edit]- α3β2-Nicotinic receptor
- α3β4-Nicotinic receptor
- α4β2-Nicotinic receptor
- RIC3, a chaperone protein for α7 receptors
- Endocannabinoids
References
[edit]- ^ a b Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5th ed., Churchill Livingstone 2003) p. 138.
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- ^ Wang, Chen; Chen, Han; Zhu, Wei; Xu, Yinchuan; Liu, Mingfei; Zhu, Lianlian; Yang, Fan; Zhang, Ling; Liu, Xianbao (January 2017). "Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 37 (1): 53–65. doi:10.1161/ATVBAHA.116.307264. ISSN 1524-4636. PMID 27834689.
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