Strychnine, Glycine, and Adrenomedullary Secretion

Abstract

Research suggests that strychnine and glycine interact with the agonist binding site of the nicotinic acetylcholine receptor (AChR) in chromaffin cells, thus exerting a pharmacological effect that may have a modulatory role on the AChR. The chromaffin cell has been extensively studied as a cholinergic neurosecretory system, and activation of the nicotinic receptor in these cells leads to the Ca 2+ dependent exocytotic release of catecholalmines, adenosine triphosphate (ATP), chromogranins, and enkephalins. These cells possess a high-affinity [ 3 H]strychnine binding site, and glycine can evoke catecholamine release from adrenomedullary tissue in vitro and in vivo , as demonstrated by the use of microdialysis techniques. The α 3 subunit of glycine receptors (but not the α 1 , or α 2 ) is expressed in rat adrenal and may mediate this effect. Strychnine inhibits the nicotinic stimulation of catecholamine release from cultured bovine adrenal chromaffin cells in a concentration-dependent (1–100 pM) manner. At 10 pM of nicotine, the IC 50 value for strychnine is approximately 30 pM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca 2+ 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.