THE ROLE OF INTRACELLULAR CALCIUM IN CATECHOLAMINE SECRETION FROM THE BOVINE ADRENAL MEDULLA

¹ Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, Lafayette, Indiana

Concentration-effect curves were obtained using isolated perfused (5 ml min : 25°C) bovine adrenals stimulated with chlorpromazine, caffeine or d-amphetamine. with and without calcium in the medium. The presence of extracellular calcium had no effect on catecholamine release by chlorpromazine or high concentrations of d-amphetamine but enhanced the response to caffeine or low concentrations of d-amphetamine. Procaine (10^-3 M) blocked the effect of extracellular calcium but had no effect on drug-evoked secretion in calcium-free medium. Magnesium (5 x 10^-3 M), by contrast, blocked drug-evoked release in time absence of calcium. Catecholamine release induced by chlorpromazine (10^-3 M), caffeine (10^-1 M) or d-amphetamine (5 x 10^-2 in calcium-free medium generally paralleled ⁴⁰Ca and ⁴⁵Ca efflux from radiocalcium-labeled glands. However, d-amphetamine initially released catecholamines without significant effect on calcium efflux, although release of both substances increased after termination of time stimulus. Chlorpromazine and caffeine mobilized ⁴⁵Ca from adrenal medullary mitochondria. Caffeine and d-amphetamine mobilized ⁴⁵Ca from the endoplasmic reticulum. It is proposed that chlorpromazine, caffeine or d-amphetamine can evoke catecholamine release by mobilizing different calcium pools within the adrenal medullary chromaffin cell and that magnesium can block this effect.