Trifluoperazine Inhibits 45Ca2+ Uptake and Catecholamine Secretion and Synthesis in Adrenal Medullary Cells

Abstract

In isolated bovine adrenal medullary cells, carbamylcholine and high K+ cause the Ca-dependent secretion of catecholamines with a simultaneous increase in the synthesis of 14C-catecholamines from [14C]tyrosine. In these cells, trifluoperazine, a selective antagonist of calmodulin, inhibited both the secretion and synthesis of catecholamines. The stimulatory effect of carbamylcholine was inhibited to a greater extent than that of high K+. The inhibitory effect of trifluoperazine on carbamylcholine-evoked secretion of catecholamines was not overcome by an increase in either carbamylcholine or Ca concentration, showing that inhibition by trifluoperazine occurs by a mechanism distinct from competitive antagonism at the cholinergic receptor and from direct inactivation of Ca channels. Doses of trifluoperazine that inhibited catecholamine secretion and synthesis also inhibited the uptake of radioactive Ca by the cells. Trifluoperazine apparently inhibits the secretion and synthesis of catecholamines mainly due to its inhibition of Ca uptake. Trifluoperazine seems to inhibit Ca uptake by uncoupling the linkage between cholinergic receptor stimulation and Ca channel activation.