Muscarinic pharmacology of the inhibition of adenylate cyclase in N18TG2 neuroblastoma cells

Abstract

This study characterizes the muscarinic cholinergic receptors associated with the inhibition of adenylate cyclase on N18TG2 neuroblastoma cell membranes. Agonists could be divided into two classes: oxotremorine, acetylcholine, carbachol and arecoline exerted the most efficacious and potent inhibition, while McN-A343, bethanechol and AHR-602 were partial agonists. Both quinuclidinyl benzilate and atropine maximally antagonized the inhibitory effect of McN-A343, carbachol and oxotremorine. Pirenzepine was almost as potent as atropine in reversing the inhibitory effect of McN-A343, but was 300 times less potent than atropine or quinuclidinyl benzilate in antagonizing the effects of either carbachol or oxotremorine. Gallamine was ineffective as an antagonist at concentrations up to 1 mM. These results suggest that the receptors that modulate this inhibition are of the M(2) type, since they were activated by carbachol, acetylcholine and oxotremorine, but much less by McN-A343 and AHR-602 (both M(1) selective agonists). The full agonists were blocked by atropine and quinuclidinyl benzilate but not by low concentrations of pirenzepine (M(1) selective antagonist).