Alpha-7 nicotinic receptor
From Wikipedia, the free encyclopedia
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.
Contents
Medical relevance[edit]
Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and alzheimers disease.[2][3][4]
An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.[5]
Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.[6]
α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.[7] α7 receptors are also involved in angiogenic activity, and have anti-apoptotic effects.[8][9]
Ligands[edit]
Agonists[edit]
- (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan- 2-carboxamide: potent and highly subtype-selective[10]
- A-582941: partial agonist; activates ERK1/2 and CREB phosphorylation; enhances cognitive performance[11]
- AR-R17779: full agonist, nootropic
- Amyloid beta: neurotoxic marker of Alzheimer's disease [12]
- TC-1698: subtype-selective; neuroprotective effects via activation of the JAK2/PI-3K cascade, neutralized by angiotensin II AT(2) receptor activation[13]
- TC-5619 - partial agonist, in development for treatment of schizophrenia
- EVP-6124 - partial agonist with nootropic properties, in development for treatment of schizophrenia and Alzheimer's disease [14][15]
- 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 [16]
- 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[17]
- SSR-180,711: partial agonist[19]
- Tropisetron: subtype-selective partial agonist; 5-HT3 receptor antagonist[20]
- WAY-317,538 - selective potent full agonist with nootropic and neuroprotective properties
- Anabasine
- Acetylcholine
- Nicotine
- Choline [21]
- ICH-3: subtype-selective partial agonist;[22]
Positive Allosteric Modulators (PAMs)[edit]
At least two types of positive allosteric modulators (PAMs) can be distinguished.[23]
- PNU-120,596[24]
- NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[25]
- 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[26] In clinical development for cognitive deficits in schizophrenia.
- A-867744[27][28]
- Ivermectin
- Galantamine
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.[32]
- Anandamide
- α-Bungarotoxin
- α-Conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible[33]
- Bupropion (very weakly)
- Dehydronorketamine
- Ethanol
- Hydroxybupropion (very weakly)
- Hydroxynorketamine
- Ketamine
- Kynurenic acid
- Memantine
- Lobeline
- Methyllycaconitine [16]
- Norketamine
- Quinolizidine (–)-1-epi-207I: α7 subtype preferring blocker[34]
See also[edit]
- α3β2-Nicotinic receptor
- α3β4-Nicotinic receptor
- α4β2-Nicotinic receptor
- RIC3, a chaperone protein for α7 receptors
- Endocannabinoids
References[edit]
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