Glutamate enhances the adenylyl cyclase-cAMP system-induced beta-endorphin secretion and POMC mRNA expression in rat hypothalamic neurons in culture: NMDA receptor-mediated modulation.
L-Glutamate, a major excitatory amino acid of the central nervous system, plays important roles as neurotransmitter and neuromodulator in the brain. Increasing evidence suggests that glutamate may also involve in the regulation of the neuroendocrine system at the hypothalamus. Employing long term monolayer hypothalamic cell cultures prepared from neonatal rats, we reported here that whereas glutamate significantly enhanced forskolin-, or N6,2'-O-dibutyryladenosine-3'5'-cyclic monophosphate [(Bu)2cAMP]-stimulated immunoreactive (ir)-beta EP release from cultures treated daily for 4 consecutive days, the excitatory amino acid alone produced little effect. This potentiation of glutamate was time-related and dose-dependent with an Emax value of the amino acid being approximately 50 microM; at this concentration glutamate augmented ir-beta EP secretion about 1.8 times (P < 0.05) that induced by 2 microM forskolin alone. Similar effects were also observed for POMC mRNA levels in cultures subjected to 6 h of the above treatment regime. This potentiating effect of glutamate appears to be mediated specifically through NMDA receptor as it can be mimicked by NMDA but not by kainic acid or quisqualic acid, and blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA glutamate receptor antagonist. Interestingly, glutamate was found not to enhance high doses of forskolin (10 microM) or (Bu)2cAMP (100 microM) stimulated beta EP release and POMC mRNA levels in hypothalamic cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Biology Unit, Mental Health Research Institute of Victoria, Royal Park Hospital, Parkville, Australia.
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Z
Yang
D L
DL
Copolov
A T
AT
Lim
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013268:Stimulation, Chemical; D001615:beta-Endorphin / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D005576:Colforsin; D018698:Glutamic Acid; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases