Effects of drugs on Ca channel and secretion of adrenal catecholamines.

Abstract

Ca plays a pivotal role in stimulus-secretion coupling in adrenal medulla. Due to the substantial Ca gradient across cell membranes, a slight increase in cell permeability to Ca causes an influx of Ca that subsequently triggers the intracellular Ca-dependent secretory processes. We investigated the effects of 1)calmodulin antagonist, 2)phospholipase A2 inhibitors and 3)α2-adrenergic agonists on the cellular influx of Ca and the secretion of catecholamine in isolated bovine adrenal medullary cells. [RESULTS] 1) Stimulation of acetylcholine receptor (ACh-R) of the cells caused a rapid and prominent influx of 45Ca that was blocked by curare, hexamethonium, but little affected by tetrodotoxin. 2) Calmodulin antagonist, trifluoperazine and phospholipase A2 inhibitors such as quinacrine, chloroquine, quinine and p-bromophenacyl bromide inhibited the influx of 45Ca by interferring with the coupling between ACh-R and Ca channel. 3) Adrenal medullary cells had α2-adrenergic receptor and stimulation of the receptor inhibited 45Ca influx caused by ACh-R stimulation. 4) These drugs, all inhibited the secretion of catecholamines at the concentrations at which they inhibited the influx of 45Ca. [CONCLUSIONS] Ca channel of adrenal medullary cells is activated via stimulation of acetylcholine receptor, and it is followed by suppression via stimulation of α2-adrenergic receptor. Calmodulin antagonist and phospholipase A2 inhibitors inhibit the cellular influx of Ca by their direct effect on cell membranes. The receptor mediated regulation of Ca channel is closely related to the regulation of catecholamine secretion. Influx of Ca into the cells is susceptible to the action of many drugs, and modification of Ca channel alters the secretion of adrenal catecholamines profoundly.