Selective Actions of Intravenous Anesthetics on Nicotinic- and Muscarinic-receptor-mediated Responses of the Dog Adrenal Medulla

Abstract

The selective actions of i.v. anesthetics on the cholinergic nicotinic and muscarinic responses of adrenal medullary cells were studied using isolated dog adrenals perfused with modified Locke''s solution. Log-probit dose-response curves of the inhibitory effects of the anesthetics on the catecholamine releases induced by acetylcholine, nicotine and muscarine were determined. Percentage inhibition by the anesthetics at clinically relevant concentrations were 98% of nicotine- and 31% of muscarine-induced releases by alfaxalone 2.6 .mu.M, 76% of nicotine and 13% of muscarine by thiopental, 23.9 .mu.M, 86% of nicotine and inhibition of muscarine by ketamine 17.0 .mu.M and no inhibition of either response by diazepam 5.0 .mu.M. The ratio of IC50 (concentration for 50% inhibition), which was calculated by dividing IC50 for muscarine by IC50 for nicotine, showed a variety of values ranging from 3.9 for diazepam to 38.0 for ketamine. Apparently each anesthetic has characteristic selective inhibitory effects on nicotinic and muscarinic cholinergic responses. The differing effects on the muscarinic responses might be one of the factors contributing to the characteristic properties of each anesthetic, while the inhibition of nicotinic responses might reflect a common property for many anesthetics.