Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors.

ABSTRACT: Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding. The affinity of NMS at the allosteric site is in the micromolar range for all receptor subtypes. Using molecular modelling of the M₂ receptor we found that E172 and E175 in the second extracellular loop and N419 in the third ex

SUBMITTER: Jakubik J 

PROVIDER: S-EPMC5238504 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature