Inhibition by ω-conotoxin GVIA of adrenal catecholamine release in response to endogenous and exogenous acetylcholine

Abstract

Effects of the N-type voltage-dependent Ca 2+ channel (VDCC) blocker, ω-conotoxin GVIA, and the L-type VDCC blockers, nifedipine and verapamil, on adrenal catecholamine release were examined in anesthetized dogs. These blockers were infused into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation at 1 and 3 Hz produced frequency-dependent increases in epinephrine and norepinephrine output determined from adrenal venous blood. Infusion of ω-conotoxin GVIA (0.4 μg/min) significantly inhibited the splanchnic nerve stimulation-evoked increases in epinephrine and norepinephrine output. Furthermore, increases in epinephrine and norepinephrine output induced by intraarterial injection of acetylcholine (3 μg) into the adrenal gland also were inhibited by ω-conotoxin GVIA (0.4 μg/min). Further inhibition of splanchnic nerve stimulation- or exogenous acetylcholine-induced increases in catecholamine output was observed even after the cessation of ω-conotoxin GVIA infusion. Neither nifedipine (1 μg/min) nor verapamil (10 μg/min) affected the splanchnic nerve stimulation-evoked increases in catecholamine output, whereas they inhibited the oxogenous acetylcholine-evoked catecholamine release. These results suggest that N-type VDCCs located in adrenal medullary cells may contribute to the release of adrenal catecholamines in response to endogenous and exogenous acetylcholine in the dog.