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The Journal of Neuroscience, March 15, 1998, 18(6):2056-2062

Metabotropic Glutamate Receptors Negatively Regulate Melatonin Synthesis in Rat Pinealocytes

Hiroshi Yamada¹, Shouki Yatsushiro¹, Shougo Ishio¹, Mitsuko Hayashi², Tsuyoshi Nishi², Akitsugu Yamamoto³, Masamitsu Futai², Akihito Yamaguchi¹, and Yoshinori Moriyama¹

Departments of ¹ Cell Membrane Biology and ² Molecular Cell Biology, Institute of Scientific and Industrial Research, Osaka University, CREST, Japan Science and Technology Corporation, Ibaraki, Osaka 567, Japan, and ³ Department of Physiology, Kansai Medical University, Moriguchi, Osaka 570, Japan

Rat pinealocytes receive noradrenergic innervation that stimulates melatonin synthesis in a cAMP-mediated manner. In addition to melatonin, we showed previously that pinealocytes secrete L-glutamate through an exocytic mechanism. The released glutamate inhibits norepinephrine (NE)-dependent melatonin synthesis. Consistent with this observation, specific agonists of class II metabotropic glutamate receptors (mGluRs), including 1-(1S,3R)-aminocyclopentane-1,3-dicarboxylic acid (tACPD), inhibited NE-dependent melatonin synthesis, whereas agonists for other types of glutamate receptors did not. Furthermore, reverse transcription-PCR, Northern blotting, and immunohistochemistry analyses indicated expression of class II mGluR3 in pinealocytes. Inhibitory guanine nucleotide-binding protein (G_i) was also detected in pinealocytes. L-Glutamate or agonists of class II receptors decreased NE- or forskolin-dependent increase of cAMP and serotonin-N-acetyltransferase activities to similar extents. These effects were blocked by pertussis toxin or dibutyryl cAMP. These results indicate that the inhibitory cAMP cascade is involved in the glutamate-evoked inhibition of melatonin synthesis. We propose that the glutaminergic system negatively regulates NE-dependent melatonin synthesis in rat pinealocytes.

Key words: melatonin; pinealocyte; metabotropic glutamate receptor; cAMP cascade; N-acetyltransferase; endocrine cell

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1862056-07$05.00/0

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