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The Journal of Neuroscience, July 1, 1998, 18(13):4946-4952

Acetylcholine Triggers L-Glutamate Exocytosis via Nicotinic Receptors and Inhibits Melatonin Synthesis in Rat Pinealocytes

Hiroshi Yamada¹, Akihiko Ogura², Shinichi Koizumi³, Akihito Yamaguchi¹, and Yoshinori Moriyama¹

¹ Department of Cell Membrane Biology, Institute of Scientific and Industrial Research (ISIR), Osaka University, Ibaraki, Osaka 567, Japan, ² Department of Biology, Osaka University Graduate School of Science, Toyonaka, Osaka 560, Japan, and ³ Novartis Pharma K. K., Takarazuka 665, Japan

Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we reported that depolarization of pinealocytes by externally added KCl and activation of L-type Ca²⁺ channels resulted in secretion of L-glutamate by microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger glutamate exocytosis under physiological conditions. Here, we report that the nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine-dependent serotonin N-acetyltransferase activity, which results in decreased melatonin synthesis. These activities were blocked by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate receptor. These results suggest that cholinergic stimulation initiates the glutaminergic signaling cascade in pineal glands and that parasympathetic neurons innervating the gland exert negative control over melatonin synthesis by way of the glutaminergic systems.

Key words: microvesicle (synaptic-like microvesicle); acetylcholine; nicotinic acetylcholine receptor (nAchR); exocytosis; glutamate; pinealocyte; pineal gland; L-type Ca²⁺ channel; serotonin N-acetyltransferase; parasympathetic neuron; melatonin synthesis

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18134946-07$05.00/0

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