PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE - CONTROL OF RAT PINEAL CYCLIC-AMP AND MELATONIN BUT NOT CYCLIC-GMP

In this study, the effects of pituitary adenylate cyclase-activating p olypeptide (PACAP) on cyclic nucleotide accumulation and melatonin (MT ) production in dispersed rat pinealocytes were measured. Treatment wi th PACAP (10(-7) M) increased MT production 2.5-fold. PACAP (10(-7) M) also increased cyclic AMP accumulation four- to fivefold; this effect was potentiated two- to threefold by alpha(1)-adrenergic activation. This potentiation appears to involve protein kinase C (PKC) because al pha(1)-adrenergic activation is known to translocate PKC and the PACAP -stimulated cyclic AMP accumulation was potentiated ninefold by a PKC activator, 4 beta-phorbol 12-myristate 13-acetate (PMA). Phenylephrine and PMA also potentiated the PACAP-stimulated MT accumulation, These results indicate that cyclic AMP is one second messenger of PACAP in t he pineal gland and that the effects of PACAP on cyclic AMP and MT pro duction can be potentiated by an alpha(1)-adrenergic --> PKC mechanism . In addition to these findings, it was observed that PACAP treatment with or without phenylephrine or PMA did not alter cyclic GMP accumula tion. This indicates that PACAP is the first ligand identified that in creases cyclic AMP accumulation in the pineal gland without increasing cyclic GMP accumulation. That PACAP fails to activate the va soactive intestinal peptide/cyclic GMP pathway suggests that the vasoactive in testinal peptide receptors present in the pineal may be distinct from the type II PACAP receptors.