Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes.
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.
Yamada
H
H
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, CREST, Japan Science and Technology Corporation, Ibaraki, Osaka 567, Japan.
Yatsushiro
S
S
Ishio
S
S
Hayashi
M
M
Nishi
T
T
Yamamoto
A
A
Futai
M
M
Yamaguchi
A
A
Moriyama
Y
Y
D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D014018:Tissue Distribution
D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D019204:GTP-Binding Proteins; D008550:Melatonin; D009638:Norepinephrine