Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes

Hiroshi Yamada, Shouki Yatsushiro, Shougo Ishio, Mitsuko Hayashi, Tsuyoshi Nishi, Akitsugu Yamamoto, Masamitsu Futai, Akihito Yamaguchi, Yoshinori Moriyama

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2056-2062
Number of pages7
JournalJournal of Neuroscience
Issue number6
Publication statusPublished - Mar 15 1998
Externally publishedYes


  • Endocrine cell
  • Melatonin
  • Metabotropic glutamate receptor
  • N- acetyltransferase
  • Pinealocyte
  • cAMP cascade

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes'. Together they form a unique fingerprint.

Cite this