Carboxyl residue(s) at the ligand-binding site of rat muscarinic receptors

Chemical modification of muscarinic receptors of rat cerebral cortex, brain stem and atria by a carboxyl-group-specific reagent, namely trimethyloxonium ion (TMO+) reduces the number of tritium-labeled antagonist- and agonist-binding sites in a dose-dependent way. No such effect is observed when modification is carried out in the presence of atropine, oxotremorine or carbamylcholine. These findings suggest that TMO+ specifically methylates the carboxyl residue(s) positioned at the binding site in members of the M1 and M2 receptor family.