PACAP stimulates catecholamine release from adrenal medulla: a novel noncholinergic secretagogue

The secretory response of the adrenal medulla to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel polypeptide with 68% structural homology to vasoactive intestinal polypeptide (VIP), was investigated in anesthetized rats by in vivo microdialysis. The injection of PACAP (1.5 nmol) caused a greater amount of increase in catecholamine concentration than carbachol (30 nmol) or VIP (30 nmol) in the dialysate for a period of 60 min. The ratios of norepinephrine to epinephrine in the dialysate after stimulation with these compounds showed no change from resting conditions. The simultaneous application of both nicotinic and muscarinic antagonists (10 mM mecamylamine and 1 mM atropine) eliminated the increase in catecholamine secretion induced by carbachol. In contrast, PACAP-induced catecholamine secretion was not inhibited by these cholinergic antagonists. These data led to the following conclusions: 1) PACAP was more potent than either carbachol or VIP in enhancing the secretion of catecholamine from the adrenal medulla, and 2) PACAP-induced catecholamine secretion was due to the direct action of PACAP on the adrenal medulla rather than an indirect action mediated by acetylcholine release. These results strongly suggest that PACAP is a noncholinergic secretagogue of the adrenal medulla in rats.