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Pituitary Adenylate Cyclase‐Activating Polypeptide: Control of Rat Pineal Cyclic AMP and Melatonin but Not Cyclic GMP
Author(s) -
Chik Constance L.,
Ho Anthony K.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64052111.x
Subject(s) - vasoactive intestinal peptide , medicine , endocrinology , adenylate kinase , pinealocyte , protein kinase c , second messenger system , cyclase , activator (genetics) , pineal gland , receptor , pituitary adenylate cyclase activating peptide , protein kinase a , phenylephrine , melatonin , chemistry , phorbol , biology , stimulation , signal transduction , neuropeptide , phosphorylation , biochemistry , blood pressure
In this study, the effects of pituitary adenylate cyclase‐activating polypeptide (PACAP) on cyclic nucleotide accumulation and melatonin (MT) production in dispersed rat pinealocytes were measured. Treatment with 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 three‐fold by α 1 ‐adrenergic activation. This potentiation appears to involve protein kinase C (PKC) because α 1 ‐adrenergic activation is known to translocate PKC and the PACAP‐stimulated cyclic AMP accumulation was potentiated ninefold by a PKC activator, 4β‐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 the pineal gland and that the effects of PACAP on cyclic AMP and MT production can be potentiated by an α 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 accumulation. This indicates that PACAP is the first ligand identified that increases cyclic AMP accumulation in the pineal gland without increasing cyclic GMP accumulation. That PACAP fails to activate the vasoactive intestinal peptide/cyclic GMP pathway suggests that the vasoactive intestinal peptide receptors present in the pineal may be distinct from the type II PACAP receptors.