Hydroxyindole-O-methyltransferase is another target for L-glutamate-evoked inhibition of melatonin synthesis in rat pinealocytes

Shougo Ishio, Hiroshi Yamada, Cheryl M. Craft, Yoshinori Moriyama

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17 Citations (Scopus)


Rat pinealocytes use L-glutamate as a modulator for melatonin synthesis. Upon binding of L-glutamate to the class II metabotropic glutamate receptor, norepinephrine (NE)-dependent formation of cAMP was inhibited, resulting in decreased serotonin-N-acetyltransferase (NAT) activity and melatonin output. Although L-glutamate at 1 mM caused 90% inhibition of melatonin synthesis, about 30% of the NAT activity remained, suggesting the presence of another target for L-glutamate. In this study, we found that L-glutamate also inhibits hydroxyindole-O-methyltransferase (HIOMT). The inhibition is reversible and dose-dependent: the maximal inhibition was obtained with more than 0.4 mM L-glutamate. Contrary to L-glutamate-evoked inhibition of NAT, agonists for class II metabotropic receptors such as (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) had no effect on HIOMT. Neither (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG), an specific antagonist for class II mGluRs, nor dibutyryl cAMP restored the L-glutamate-evoked inhibition of HIOMT. Northern blot analyses revealed that L-glutamate significantly inhibits the expression of mRNA of NAT, but not that of HIOMT. These results indicated that HIOMT is an another target for L-glutamate due to its inhibition of melatonin synthesis, and the signaling pathway toward the inhibition is distinct from that of NAT. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalBrain Research
Issue number1-2
Publication statusPublished - Dec 11 1999


  • Hydroxyindole-O-methyltransferase
  • L-Glutamate
  • Melatonin
  • Pinealocyte
  • Serotonin-N-acetyltransferase

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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