Actions of membrane-active drugs on agonist occupation and functional state of nicotinic acetylcholine receptors

The activities of 3 inhibitors of the nicotinic Ach receptor were examined for their capacity to affect agonist-elicited permeanbility and agonist occupation of the receptor in intact BC3H-1 cells. Nicardipine, dansylpropranolog and propranolol all inhibited receptor function in a manner which was non-competitive with agonist. Each enhanced the affinity of carbachol for the receptor as do the local anesthetics which promote receptor desensitization. Comparisons of the agonist binding functions with the state functions for desensitization of the permeability response in the presence of the 3 inhibitors showed that at least part of the non-competitive action arised from the enhancement of receptor desensitization. For nicardipine, the block of agonist-elicited Na+ and Ca++ permeabilities occurred over identical concentration rangs which indicates that the antagonism is not ion-specific.