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

We elucidated the contribution of endogenous pituitary adenylate cyclase-ac tivating polypeptide (PACAP) to neurally evoked catecholamine secretion fro m the isolated perfused rat adrenal gland. Infusion of PACAP (100 nM) incre ased adrenal epinephrine and norepinephrine output. The PACAP-induced catec holamine output responses were inhibited by the PACAP type I receptor antag onist PACAP( 6-38) (30-3,000 nM) but were resistant to the PACAP type II re ceptor antagonist [Lys(1), Pro(2,5), Ara(3,4),Tyr(6)]- vasoactive intestina l 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 nor epinephrine output. PACAP-(6-38) (3,000 nM), but not LPAT-VIP, also inhibit ed the ES-induced catecholamine output responses. However, PACAP-(6-38) did not affect the ACh-induced catecholamine output responses. PACAP at low co ncentrations (0.3-3 nM), which had no influence on catecholamine output, en hanced the ACh-induced catecholamine output responses, but not the ES-induc ed catecholamine output responses. These results suggest that PACAP is rele ased from the nerve endings to facilitate the neurally evoked catecholamine secretion through PACAP type I receptors in the rat adrenal gland.