Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells

Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration‐dependent (1–100 μm) manner. At 10 μm nicotine, the IC₅₀ value for strychnine is approximately 30 μm. Strychnine also inhibits the nicotine‐induced membrane depolarization and increase in intracellular Ca²⁺ concentration. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K⁺ concentration, histamine or angiotensin II. Strychnine competes with nicotine in its effect, but does not modify the apparent positive cooperativity of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release. These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. 1994 British Pharmacological Society