INTERACTION BETWEEN ADRENERGIC AND PEPTIDE STIMULATION IN THE RAT PINEAL, PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE

The 27 amino acid peptide, pituitary adenylate cyclase-activating poly peptide (PACAP-27), and its 38 amino acid analogue, PACAP-38, stimulat e serotonin-N-acetyltransferase (NAT) activity and N-acetylserotonin ( NAS) and melatonin content of pineal glands from adult rats. Maximal s timulation of rat pineal NAT by PACAP-38 is not increased further sign ificantly by concurrent stimulation with the two related peptides, vas oactive intestinal polypeptide (VIP) and/or peptide N-terminal histidi ne C-terminal isoleucine (PHI), Isoproterenol was a more potent induce r of NAT activity than any of these peptides alone or in combination. PACAP-38 also stimulates melatonin production by chicken pineal cells in culture as does VIP. Stimulation by both was not greater than after either alone. Prior stimulation of rat pineal NAT activity with VIP, PHI, or PACAP-38 reduces the magnitude of subsequent stimulation with PACAP-38 or forskolin, Concurrent stimulation of alpha-receptors or tr eatment with active phorbol ester augments rat pineal response to PACA P-38 stimulation just as it increases the response to VIP, PHI, and be ta-receptor stimulation. Pineals from newborn rats respond to PACAP-38 with an increase in NAT activity and the increase is augmented by con comitant alpha(1)-adrenergic stimulation. The putative PACAP inhibitor PACAP (6-38) and the putative VIP inhibitor (Ac-Tyr,D-Phe)-GRF 1-29 a mide, in 100-1,000-fold excess, did not affect the stimulatory activit y of any of the peptides, Pineal melatonin concentration parallels cha nges in pineal NAT activity.