Role of endogenous PACAP in catecholamine secretion from the rat adrenal gland

1 Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578; and 2 Department of Dental Pharmacology, The Nippon Dental University School of Dentistry at Niigata, Hamaura-cho, Niigata 951-8580, Japan We elucidated the contribution of endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) to neurally evoked catecholamine secretion from the isolated perfused rat adrenal gland. Infusion of PACAP (100 nM) increased adrenal epinephrine and norepinephrine output. The PACAP-induced catecholamine output responses were inhibited by the PACAP type I receptor antagonist PACAP- (6-38) (30-3,000 nM) but were resistant to the PACAP type II receptor antagonist [Lys 1 ,Pro 2,5 ,Ara 3,4 ,Tyr 6 ]-vasoactive intestinal peptide (LPAT-VIP; 30-3,000 nM). Transmural electrical stimulation (ES; 1-10 Hz) or infusion of ACh (6-200 nM) increased adrenal epinephrine and norepinephrine output. PACAP-(6-38) (3,000 nM), but not LPAT-VIP, also inhibited the ES-induced catecholamine output responses. However, PACAP-(6-38) did not affect the ACh-induced catecholamine output responses. PACAP at low concentrations (0.3-3 nM), which had no influence on catecholamine output, enhanced the ACh-induced catecholamine output responses, but not the ES-induced catecholamine output responses. These results suggest that PACAP is released from the nerve endings to facilitate the neurally evoked catecholamine secretion through PACAP type I receptors in the rat adrenal gland. transmural electrical stimulation; acetylcholine; pituitary adenylate cyclase-activating polypeptide receptor antagonists; pituitary adenylate cyclase-activating polypeptide -(6-38); adrenal chromaffin cells