Alpha-7 nicotinic receptor


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. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric .
It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields post- and presynaptic excitation, mainly by increased Ca2+ permeability.
Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina. Functional α7 receptors are present in the submucous plexus neurons of the guinea-pig ileum.

Medical relevance

The Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and Alzheimer's disease.
The α7 receptor is highly implicated in the efficacy of Varenicline for smoking cessation therapy significantly more than α4β2 which is responsible for Nicotine's rewarding effects. Upregulation of α7-nAChR's is greatly correlated with a stronger response.
An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.
Activation of α7 nicotinic acetylcholine receptor on mast cells, is a mechanism by which nicotine enhances atherosclerosis.
Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.
α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis. α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects.

Ligands

Agonists

At least two types of positive allosteric modulators can be distinguished.
  • PNU-120,596
  • NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant
  • 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 In clinical development for cognitive deficits in schizophrenia.
  • A-867744
  • Ivermectin

    Other

  • Nefiracetam

    Antagonists

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.