INHIBITORY EFFECT OF STRYCHNINE ON ACETYLCHOLINE-RECEPTOR ACTIVATION IN BOVINE ADRENAL-MEDULLARY CHROMAFFIN CELLS

1 Strychnine, which is known as a potent and selective antagonist of t he inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultur ed adrenal chromaffin cells in a concentration-dependent (1-100 mu M) manner. At 10 mu M nicotine, the IC50 value for strychnine is approxim ately 30 mu M. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2 The inhibitory action of strychnine is reversible and is selective for ni cotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3 Stryc hnine competes with nicotine in its effect, but does not modify the ap parent positive cooperativity of the nicotine binding sites. In the ab sence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory actio n of strychnine on this release, 4 These results suggest that strychni ne interacts with the agonist binding site of the nicotinic acetylchol ine receptor in chromaffin cells, thus exerting a pharmacological effe ct independently of the glycine receptor.