Differential Effects of D 600 on Release of Catecholamines by Acetylcholine, Histamine, Tyramine and by Cyclic AMP from Canine Adrenal Medulla.

Abstract

The isolated canine adrenal glands were perfused retrogradely with Locke''s solution, and the catecholamine contents of the effluents were measured by the trihydroxyindole-fluorimetric method. Stimulation of the glands by acetylcholine, histamine, tyramine and cyclic[c]AMP increased catecholamine release from the glands. Introduction of D 600 [methoxyverapamil] to the perfusion medium reduced release of catecholamines in response to acetylcholine, and this reduction was overcome by raising Ca2+ concentrations of the perfusion medium. Similarly, D 600 reduced release of catecholamines in response to histamine. The release of catecholamines evoked by tyramine was inhibited by D 600, although to a lesser degree than the release by acetylcholine. D 600 was entirely ineffective on the catecholamine release in response to cAMP. D 600 had no effect on the spontaneous catecholamine output. Release of catecholamines from adrenal chromaffin cells by acetylcholine and histamine, and by tyramine in part requires the entry of Ca ions across the cell membrane, whereas that by cAMP does not.