Microvesicle-mediated exocytosis of glutamate is a novel paracrine-like chemical transduction mechanism and inhibits melatonin secretion in rat pinealocytes

Hiroshi Yamada, Akitsugu Yamamoto, Susumu Yodozawa, Shunji Kozaki, Masami Takahashi, Mitsuhiro Morita, Hitoshi Michibata, Teiichi Furuichi, Katsuhiko Mikoshiba, Yoshinori Moriyama

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


Mammalian pinealocytes are neuroendocrine cells that synthesize and secrete melatonin, these processes being positively controlled by norepinephrine derived from innervating sympathetic neurons. Previously, we showed that pinealocytes contain a large number of microvesicles (MVs) that specifically accumulate L-glutamate through a vesicular glutamate transporter and contain proteins for exocytosis such as synaptobrevin 2 (VAMP2). These findings suggested that the MVs are counterparts of synaptic vesicles and are involved in paracrine-like chemical transduction in the pineal gland. Here, we show that pinealocytes actually secrete glutamate upon stimulation by KCl in the presence of Ca2+ at 37°C. The ability of glutamate secretion disappeared when the cells were incubated at below 20°C. Loss of the activity was also observed on successive stimulation, but it was recovered after 12 hr incubation. A low concentration of cadmium chloride or ω-conotoxin GVIA inhibited the secretion. Botulinum neurotoxin E cleaved synaptic vesicle-associated protein 25 (SNAP-25) and thus inhibited the secretion. The released L-glutamate stimulated pinealocytes themselves via glutamate receptor(s) and inhibited norepinephrine-stimulated melatonin secretion. These results strongly suggest that pinealocytes are glutaminergic paraneurons, and that the glutaminergic system regulates negatively the synthesis and secretion of melatonin. The MV-mediated paracrine-like chemical transduction seems to be a novel mechanism that regulates hormonal secretion by neuroendocrine cells.

Original languageEnglish
Pages (from-to)175-191
Number of pages17
JournalJournal of Pineal Research
Issue number3
Publication statusPublished - Oct 1996
Externally publishedYes


  • Chemical transaction
  • Glutamate receptors
  • L-glutamate
  • Melatonin
  • Microvestcles
  • Paracrine
  • Paraneuron
  • Pineal gland

ASJC Scopus subject areas

  • Endocrinology


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