ACETYLCHOLINE TRIGGERS L-GLUTAMATE EXOCYTOSIS VIA NICOTINIC RECEPTORSAND INHIBITS MELATONIN SYNTHESIS IN RAT PINEALOCYTES

Rat pinealocytes, melatonin-secreting endocrine cells, contain periphe ral glutaminergic systems. L-Glutamate is a negative regulator of mela tonin synthesis through a metabotropic receptor-mediated inhibitory cA MP cascade. Previously, we reported that depolarization of pinealocyte s by externally added KCl and activation of L-type Ca2+ channels resul ted in secretion of L-glutamate by microvesicle exocytosis. What is un known is how and what kinds of stimuli trigger glutamate exocytosis un der physiological conditions. Here, we report that the nicotinic acety lcholine receptor can trigger glutamate exocytosis from cultured rate pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinphr ine-dependent serotonin N-acetyltransferase activity, which results in decreased melatonin synthesis. These activities were blocked by (2S,3 S,4S)-2-methyl-2- (carboxycyclopropyl)glycine, an antagonist of the me tabotropic glutamate receptor. These results suggest that cholinergic stimulation initiates the glutaminergic signaling cascade in pineal gl ands and that parasympathetic neurons innervating the gland exert nega tive control over melatonin synthesis by way of the glutaminergic syst ems.