Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes

J Neurosci. 1998 Mar 15;18(6):2056-62. doi: 10.1523/JNEUROSCI.18-06-02056.1998.

Abstract

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 (Gi) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cells, Cultured
  • GTP-Binding Proteins / metabolism
  • Glutamic Acid / pharmacology
  • Melatonin / antagonists & inhibitors
  • Melatonin / biosynthesis*
  • Norepinephrine / pharmacology
  • Pineal Gland / cytology
  • Pineal Gland / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / physiology*
  • Tissue Distribution

Substances

  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • GTP-Binding Proteins
  • Melatonin
  • Norepinephrine