Mechanism of the effect of droperidol to induce catecholamine efflux from the adrenal medulla.

The study was undertaken to determine whether droperidol had an effect to induce catecholamine efflux from the adrenal medulla as a mechanism for the possible pressor effect of droperidol in patients with pheochromocytoma and, if so, to ascertain the site of action of this compound. The efflux of catecholamines from perfused dog adrenals was increased from control level, 0.15 micrograms/min, to 0.66 micrograms/min by the administration of droperidol 6.6 microM. This effect of droperidol was not dependent on extracellular Ca++, in contrast to acetylcholine. The concomitant secretion of catecholamines and dopamine-beta-hydroxylase was observed in response to acetylcholine and caffeine. However, droperidol-, histamine-, and reserpine-induced catecholamine efflux was not accompanied by dopamine-beta-hydroxylase release. In additional studies, chromaffin granules were isolated with a Millipore filter technique from the bovine adrenal medulla and were incubated for 10 min in an isotonic medium to examine the direct effects of droperidol. Droperidol did not enhance the efflux of catecholamines from the granules in contrast to histamine. The uptake of 14C-norepinephrine into the granules was inhibited by droperidol in a manner comparable to reserpine. The results suggest that droperidol induces catecholamine efflux from adrenal medullary cells and the efflux probably is caused by a nonexocytotic mechanism. A contributing mechanism was an inhibition of catecholamine uptake into chromaffin granules, resulting in an increased diffusion of catecholamines out of the cell.