Vasoactive intestinal peptide stimulates melatonin release from perifused pineal glands of rats

  • V. Simonneaux
  • A. Ouichou
  • P. Pévet
Full Papers


The rat pineal gland is known to release melatonin in response to noradrenergic stimulation. The effect of vasoactive intestinal peptide (VIP), one of the neuropeptides present in the pineal, was examined on perifused rat pineal glands. VIP stimulated melatonin release with a dose-dependent effect above 10−7 M. In regard of kinetic characteristics, the pattern of melatonin release after VIP stimulation was similar to that after isoproterenol stimulation. 10−6 M VIP-stimulated melatonin release was not altered when the pineal glands were treated with 10−5 M propranolol (a β-adrenergic antagonist) or 10−5 M prazosin (an α1-adrenergic antagonist). Thus VIP has a noradrenergic-independent effect on melatonin secretion. Conversely, this VIP effect is greatly inhibited by the specific action of a VIPergic antagonist. This suggests that VIP acts on melatonin synthesis through its own binding sites.

This study demonstrates that melatonin secretion from rat pineal glands may be elicited through a VIPergic system which is independent of the well-known noradrenergic system.


VIP pineal gland melatonin rat and perifusion 


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  1. Axelrod J, Shein HM, Wurtman RJ (1969) Stimulation of14C-melatonin synthesis from14C-tryptophan by noradrenaline in rat pineal organ culture. Proc Natl Acad Sci USA 62: 544–549PubMedGoogle Scholar
  2. Axelrod J (1974) The pineal gland: a neurochemical transducer. Science 184: 1341–1348PubMedGoogle Scholar
  3. Besson J, Sarrieau A, Vial M, Marie JC, Rosselin G, Rostene W (1986) Characterization and autoradiographic distribution of vasoactive intestinal peptide binding sites in the rat control nervous system. Brain Res 398: 329–336PubMedGoogle Scholar
  4. Browstein M, Axelrod J (1974) Pineal gland: 24 hours rhythm in norepinephrine turnover. Science 184: 163–165PubMedGoogle Scholar
  5. Buijs RM, Pévet P (1980) Vasopressinand oxytocin-containing fibres in the pineal gland and subcommissural organ of the rat. Cell Tissue Res 205: 11–17PubMedGoogle Scholar
  6. Evered D, Clark S (1985) Photoperiodism, melatonin and the pineal. Ciba Foundation Symposium. LondonGoogle Scholar
  7. Fraser S, Cowen P, Franklin M, Franey C, Arendt J (1983) Direct radio-immunoassay for melatonin in plasma. Clin Chem 29: 396–397PubMedGoogle Scholar
  8. Gespach C, Bawab W, Chastre E, Emani S, Yanaihara N, Rosselin G (1988) Pharmacology and molecular identification of vasoactive intesinal peptide (VIP) receptors in normal and cancerous gastric mucosa in man. Biochem Biophys Res Commun 151: 939–947PubMedGoogle Scholar
  9. Harper JF (1984) Peritz' F test: basic program of a robust multiple comparison test for statistical analysis of all differences among group means. Comp Biol Med 14: 437–445Google Scholar
  10. Hökfelt T, Schultzberg M, Lundberg M, Fuxe K, Mutt V, Fahrenkrug J, Said SI (1982) Distribution of vasoactive intestinal polypeptide in the central and peripheral nervous system as revealed by immunocytochemistry. In: Said SI (ed) Vasoactive intestinal peptide. Advances in peptide hormone research. Raven Press, New York, pp 65–90Google Scholar
  11. Kaku K, Inoue Y, Matsutani A, Okubo M, Hatao K, Kaneko T, Yanaihara N (1983) Receptors for vasoactive intestinal polypeptide on rat dispersed pineal cells. Biomed Res 4: 321–328Google Scholar
  12. Kaku K, Tsuchiya M, Matsuda M, Inoue Y, Kaneko T, Yanaihara N (1985) Light and agonist alter vasoactive intestinal peptide binding and intracellular accumulation of adenosine 3′,5′-monophosphate in the rat pineal gland. Endocrinology 117: 2371–2375PubMedGoogle Scholar
  13. Kaku K, Tsuchiya M, Tanizawa Y, Okuya S, Inoue Y, Kaneko T, Yanaihara N (1986) Circadian cycles in VIP content and VIP stimulation of cyclic AMP accumulation in the rat pineal gland. Peptides 7 [Suppl 1]: 193–195PubMedGoogle Scholar
  14. Kaneko T, Cheng PY, Oka H, Oda T, Yanaihara N, Yanaihara C (1980) Vasoactive intestinal polypeptide stimulates adenylate cyclase and serotonin N-acetyl transferase activities in rat pineal in vitro. Biomed Res 1: 84–87Google Scholar
  15. Klein DC, Weller JL, Moore RY (1971) Melatonin metabolism: neural regulation of pineal serotonin: acetyl coenzym. A N-acetyl transferase activity. Proc Natl Acad Sci USA 68: 3107–3110PubMedGoogle Scholar
  16. Klein DC, Auerbach DA, Namboodiri MAA, Wheler GHT (1981) Indole metabolism in the mammalian pineal gland. In: Reiter RJ (ed) The pineal gland, vol 1. Anatomy and biochemistry. CRC Press, Boca Raton, Florida, pp 199–227Google Scholar
  17. Korf HW, Møller M (1985) The central innervation of the mammalian pineal organ. In: Mess B, Rúzsás Cs, Tima L, Pévet P (eds) The pineal gland, current state of pineal research. Akademiai Kiado, Budapest, pp 47–69Google Scholar
  18. Mezey E, Kiss JZ (1985) Vasoactive intestinal peptide-containing neurons in the para-ventricular nucleus may participate in regulating prolactin secretion. Proc Natl Acad Sci USA 82: 245–247PubMedGoogle Scholar
  19. Mikkelsen JD, Korf HW, Møller M (1987) Vasoactive intestinal peptide (VIP) in the pineal gland of the rat. In: Trentini GP, De Gaetani C, Pévet P (eds) Fundamental and clinics in pineal research. Raven Press, New York, pp 87–90Google Scholar
  20. Møller M, Fahrenkrug J, Ottensen B (1981) The presence of vasoactive intestinal peptide (VIP) in nerve fibres connecting the brain and the pineal gland of the cat. EPSG Newslett [Suppl] 3: 45Google Scholar
  21. Møller M, Mikkelsen JD, Fahrenkrug J, Korf HW (1984) Autoradiographical localization of VIP-receptors in the brain and pineal gland of rat and gerbil. EPSG Newslett [Suppl] 5: 38Google Scholar
  22. Møller M, Mikkelsen JD, Fahrenkrug J, Korf HW (1985) The presence of vasoactive intestinal polypeptide (VIP)-like-immunoreactive nerve fibres and VIP-receptors in the pineal gland of the Mongolian gerbil (Meriones unguiculatus). An immunohistochemical and receptor-autoradiographic study. Cell Tissue Res 241: 333–340PubMedGoogle Scholar
  23. Møller M, Cozzi B, Schröder H, Mikkelsen JD (1987) The peptidergic innervation of the mammalian pineal gland. In: Trentini GP, De Gaetani C, Pévet P (eds) Fundamental and clinics in pineal research. Raven Press, New York, pp71–77Google Scholar
  24. Morgan PJ, Williams LM, Lawson W, Riddoch G (1988) Adrenergic and VIP stimulation of cyclic AMP accumulation in ovine pineals. Brain Res 447: 279–286PubMedGoogle Scholar
  25. Nürnberger F, Korf HW (1981) Oxytocin- and vasopressin-immunoreactive nerve fibers in the pineal gland of the hedgehog,Erinaceus europaeus L. Cell Tissue Res 220: 87–97PubMedGoogle Scholar
  26. Pévet P (1986) The different classes of pineal peptides: origin and probable physiological role during development. In: Gupta D, Reiter RJ (eds) The pineal gland during development from fetus to adult. Groom Helm, London, pp 234–247Google Scholar
  27. Pévet P (1987) Environmental control of the annual reproductive cycle in mammals. Role of the pineal gland. In: Pévet P (ed) Comparative physiology of environmental adaptations. III. Adaptations to climatic changes. Karger, Basel, pp 82–100Google Scholar
  28. Reiter RJ (1986) Annual cycle of reproduction in mammals: adaptative mechanisms involving the photoperiod and the pineal gland. In: Assenmacher I, Boissin J (eds) Endocrine regulations as adaptatice mechanisms to the environment. CNRS, Paris, pp 161–170Google Scholar
  29. Rønnekleiv OK, Kelly MJ (1984) Distribution of substance P neurons in the epithalamus of the rat: an immunohistochemical investigation. J Pineal Res 1: 355–370PubMedGoogle Scholar
  30. Said SI, Mutt V (1970) Polypeptide with broad biological activity: isolation from small intestine. Science 169: 1217–1218PubMedGoogle Scholar
  31. Said SI, Mutt V (1972) Isolation from porcine intestinal wall of a vasoactive octacosapeptide related to secretion and to glucagon. Eur J Biochem 28: 199–204PubMedGoogle Scholar
  32. Said SI, Mutt V (1988) Vasoactive intestinal peptide and related peptides. Ann NY Acad Sci, vol 527. New York, p 691Google Scholar
  33. Shiotani Y, Yamano M, Shiosaka S, Emson PC, Hillyard CJ, Girgis S, MacIntyre I (1986) Distribution and origins of substance P (SP)-, calcitonin gene-related peptide (CGRP)- vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing fibers in the pineal gland of gerbils. Neursci Lett 70: 187–192Google Scholar
  34. Simonneaux V, Ouichou A, Pévet P, Masson-Pévet M, Vivien-Roëls B, Vaudry H (1989) Kinetic study of melatonin release from rat pineal glands using a perifusion technique. J Pineal Res (in press)Google Scholar
  35. Susuki Y, McMaster D, Lederis K, Rorstad OP (1984) Characterization of the relaxant effects of vasoactive intestinal peptide (VIP) and PHI on isolated brain arteries. Brain Res 322: 9–16PubMedGoogle Scholar
  36. Taylor DP, Pert CB (1979) Vasoactive intestinal polypeptide: specific binding to rat brain membranes. Proc Natl Acad Sci USA 76: 660–664PubMedGoogle Scholar
  37. Tonon MC, Leroux P, Stoeckel ME, Jegou S, Pelletier G, Vaudry H (1983) Catecholaminergic control of α-melanocyte-stimulating hormone (α-MSH) release from frog neurointermediate lobe in vitro: evidence for direct stimulation of α-MSH release by thyrotrophin-release hormone. Endocrinology 112: 133–141PubMedGoogle Scholar
  38. Uddman R, Alumets J, Hakanson R, Loren I, Sundler F (1980 a) Vasoactive intestinal peptide (VIP) occurs in nerves of the pineal gland. Experientia 39: 1119–1120Google Scholar
  39. Uddman R, Alumets J, Ehinger B, Hakanson R, Loren I, Sundler F (1980b) Vasoactive intestinal peptide nerves in ocular and orbital structures of the cat. Invest Ophtalm Vis Sci 19: 878–885Google Scholar
  40. Yuwiller A (1983 a) Light and agonists alter pineal N-acetyltransferase induction by vasoactive intestinal polypeptide. Science 220: 1082–1083PubMedGoogle Scholar
  41. Yuwiller A (1983 b) Vasoactive intestinal peptide stimulation of pineal serotonin-N-acetyltransferase activity: general characteristics. J Neurochem 41: 146–153PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • V. Simonneaux
    • 1
  • A. Ouichou
    • 1
  • P. Pévet
    • 1
  1. 1.CNRS URA 1332 “Neurobiologie des Fonctions Rythmiques et Saisonnières”, Laboratoire de ZoologieUniversité Louis PasteurStrasbourgFrance

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