Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and inhibits melatonin synthesis in rat pinealocytes

Hiroshi Yamada, Akihiko Ogura, Shinichi Koizumi, Akihito Yamaguchi, Yoshinori Moriyama

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59 Citations (Scopus)


Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we reported that depolarization of pinealocytes by externally added KCI and activation of L-type Ca2+ channels resulted in secretion of L-glutamate by microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger glutamate exocytosis under physiological conditions. Here, we report that the nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine-dependent serotonin N- acetyltransferase activity, which results in decreased melatonin synthesis. These activities were blocked by (2S,3S,4S)-2methyl-2- (carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate receptor. These results suggest that cholinergic stimulation initiates the glutaminergic signaling cascade in pineal glands and that parasympathetic neurons innervating the gland exert negative control over melatonin synthesis by way of the glutaminergic systems.

Original languageEnglish
Pages (from-to)4946-4952
Number of pages7
JournalJournal of Neuroscience
Issue number13
Publication statusPublished - Jul 1 1998
Externally publishedYes


  • Acetylcholine
  • Exocytosis
  • Glutamate
  • L-type Ca channel
  • Melatonin synthesis
  • Microvesicle (synaptic-like microvesicle)
  • Nicotinic acetylcholine receptor (nAchR)
  • Parasympathetic neuron
  • Pineal gland
  • Pinealocyte
  • Serotonin N-acetyltransferase

ASJC Scopus subject areas

  • Neuroscience(all)


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