Stable desensitization of α₇ nicotinic acetylcholine receptors by NS6740 requires interaction with S36 in the orthosteric agonist binding site.

ABSTRACT: NS6740 is an α₇ nicotinic acetylcholine receptor-selective partial agonist with low efficacy for channel activation, capable of promoting the stable conversion of the receptors to nonconducting (desensitized) states that can be reactivated with the application of positive allosteric modulators (PAMs). In spite of its low efficacy for channel activation, NS6740 is an effective activator of the cholinergic anti-inflammatory pathway. We observed that the concentration-response relationships for channel activation, both when applied alone and when co-applied with the PAM PNU-120596 are inverted-U shaped with inhibitory/desensitizing activities dominant at high concentrations. We evaluated the potential importance of recently identified binding sites for allosteric activators and tes

SUBMITTER: Pismataro MC 

PROVIDER: S-EPMC8478151 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature