title: Pharmacological, molecular and functional characterization of vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptors in the rat pineal gland.
abstract: Melatonin secretion from the mammalian pineal gland is strongly stimulated by noradrenaline and also by vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Three types of receptors for VIP and PACAP have been characterized so far: VIP1/PACAP receptors and VIP2/PACAP receptors, which possess similar high affinities for VIP and PACAP, and PACAP1 receptors which exhibit a 100-1000-fold higher affinity for PACAP. The aim of the present study was to characterize the receptor subtype(s) mediating the stimulatory effects of VIP and PACAP on melatonin synthesis in the rat pineal gland. Autoradiographic studies showed that PACAP and VIP were equally potent in displacing binding of radioiodinated PACAP27 from pineal sections. Amplification of pineal complementary DNAs by polymerase chain reaction using specific primers for the different receptor subtypes revealed that all three receptor messenger RNAs are expressed and that VIP1/PACAP receptor messenger RNA was predominant over VIP2/PACAP receptor messenger RNA. In vitro, VIP and PACAP stimulated melatonin synthesis with similar high potency and the effect of the two peptides were not additive. The selective VIP1/PACAP receptor agonists [R16]chicken secretin (1-25) and [K15, R16, L27]VIP(1-7)/growth hormone releasing factor(8-27) were significantly more potent than the selective VIP2/PACAP receptor agonist RO 25-1553 in stimulating melatonin secretion. The stimulatory effects of VIP and PACAP were similarly inhibited by the VIP1/PACAP antagonist [acetyl-His1, D-Phe2, K15, R16, L27]VIP(3-7)/growth hormone releasing factor(8-27). These data strongly suggest that VIP and PACAP exert a stimulatory effect on melatonin synthesis mainly through activation of a pineal VIP1/PACAP receptor subtype.
authors.affiliation: Laboratoire de Neurobiologie des Fonctions Rythmiques et Saisonnières, URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
authors.forename: V
authors.initials: V
authors.lastname: Simonneaux
authors.forename: P
authors.initials: P
authors.lastname: Kienlen-Campard
authors.forename: J P
authors.initials: JP
authors.lastname: Loeffler
authors.forename: M
authors.initials: M
authors.lastname: Basille
authors.forename: B J
authors.initials: BJ
authors.lastname: Gonzalez
authors.forename: H
authors.initials: H
authors.lastname: Vaudry
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
authors.forename: P
authors.initials: P
authors.lastname: Pévet
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001993:Bronchodilator Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000502:physiology; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010870:Pineal Gland / Q000737:chemistry* / Q000201:enzymology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C495403:Adcyap1 protein, rat; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D007457:Iodine Radioisotopes; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C110307:PG 97-269; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases; D008550:Melatonin; D007545:Isoproterenol