METABOTROPIC GLUTAMATE RECEPTORS NEGATIVELY REGULATE MELATONIN SYNTHESIS IN RAT PINEALOCYTES

Rat pinealocytes receive noradrenergic innervation that stimulates mel atonin 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, spe cific agonists of class II metabotropic glutamate receptors (mGluRs), including 1-(1S,3R)-aminocyclopentane-1,3-dicarboxylic acid (tACPD), i nhibited NE-dependent melatonin synthesis, whereas agonists for other types of glutamate receptors did not. Furthermore, reverse transcripti on-PCR, Northern blotting, and immunohistochemistry analyses indicated expression of class II mGluR3 in pinealocytes. Inhibitory guanine nuc leotide-binding protein (G(i)) was also detected in pinealocytes. L-Gl utamate or agonists of class II receptors decreased NE- or forskolin-d ependent 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 cascad e is involved in the glutamate-evoked inhibition of melatonin synthesi s, We propose that the glutaminergic system negatively regulates NE-de pendent melatonin synthesis in rat pinealocytes.