Pharmacological, molecular and functional characterization of vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptors in the rat pineal gland

• Published in: Neuroscience 1998-08, Vol.85 (3), p.887-896
• Main Authors: Simonneaux, V, Kienlen-Campard, P, Loeffler, J.-P, Basille, M, Gonzalez, B.J, Vaudry, H, Robberecht, P, Pévet, P
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Adrenergic beta-Agonists - pharmacology; Animals; Autoradiography; Biological and medical sciences; Bronchodilator Agents - pharmacology; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Gene Expression - physiology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Iodine Radioisotopes; Isoproterenol - pharmacology; Male; melatonin; Melatonin - metabolism; Neuropeptides - pharmacology; Neurotransmitter Agents - pharmacology; Peptide Fragments - pharmacology; Peptides, Cyclic - pharmacology; pineal gland; Pineal Gland - chemistry; Pineal Gland - enzymology; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Wistar; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone - analysis; Receptors, Pituitary Hormone - genetics; Receptors, Pituitary Hormone - metabolism; Receptors, Vasoactive Intestinal Peptide - analysis; Receptors, Vasoactive Intestinal Peptide - genetics; Receptors, Vasoactive Intestinal Peptide - metabolism; RNA, Messenger - analysis; Signal Transduction - drug effects; Signal Transduction - physiology; Vasoactive Intestinal Peptide - analogs & derivatives; Vasoactive Intestinal Peptide - pharmacology; vasoactive intestinal polypeptide; Vertebrates: endocrinology; VIP agonist; VIP antagonist
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(97)00668-4

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: VIP 1/PACAP receptors and VIP 2/PACAP receptors, which possess similar high affinities for VIP and PACAP, and PACAP 1 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 VIP 1/PACAP receptor messenger RNA was predominant over VIP 2/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 VIP 1/PACAP receptor agonists [R 16]chicken secretin (1–25) and [K 15, R 16, L 27]VIP(1–7)/growth hormone releasing factor(8–27) were significantly more potent than the selective VIP 2/PACAP receptor agonist RO 25–1553 in stimulating melatonin secretion. The stimulatory effects of VIP and PACAP were similarly inhibited by the VIP 1/PACAP antagonist [acetyl-His 1, D-Phe 2, K 15, R 16, L 27]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 VIP 1/PACAP receptor subtype.