Inhibitory action of carvedilol, a novel alpha, beta-adrenoceptor antagonist, on catecholamine secretion and calcium influx in cultured bovine adrenal chromaffin cells

The effect of carvediolol on the secretory function was studied using cultured bovine adrenal chromaffin cells. Carvedilol caused the concentration-dependent inhibition of catecholamine secretion evoked by carbamylcholine, high K+ or veratridine. The drug also caused the inhibition of radioactive calcium uptake stimulated by these secretagogues into the cells, and the inhibition of calcium uptake was observed in parallel with that of catecholamine secretion. The inhibitory action of carvedilol on catecholamine secretion was shown to be similar to that caused by a classical beta-adrenoceptor antagonist, propranolol. Furthermore, although the level of carbamylcholine-stimulated catecholamine secretion inhibited by diltiazem, a potent calcium channel antagonist, was significantly raised by elevating the calcium concentration in the reaction mixture, increasing the concentration of calcium ions in the mixture failed to induce any substantial influence on the secretion inhibited by carvedilol, as well as propranolol, under the same experimental conditions. These results seem to indicate that carvedilol may cause the inhibition of catecholamine secretion through its blocking action on calcium influx into the cells, and suggest the possibility that the inhibitory action of carvedilol on calcium influx is presumably based on its stabilizing action on the plasma membranes rather than its blocking action on the calcium channels in the chromaffin cell.