Inhibitory effect of glutamate release from rat cerebrocortical nerve terminals by resveratrol.
We examined the effect of resveratrol, a natural polyphenol, on the release of endogenous glutamate from nerve terminals purified from rat cerebral cortex. Result showed that the release of glutamate evoked by 4-aminopyridine (4-AP) was inhibited by resveratrol in a concentration-dependent manner. Further experiments reveal that resveratrol-mediated inhibition of glutamate release: (i) resulted from a reduction of vesicular exocytosis, not from an inhibition of non-vesicular release; (ii) was not due to an alternation of nerve terminal excitability; (iii) was associated with a decrease in presynaptic N- and P/Q-type voltage-dependent Ca(2+) channel activity; and (iv) appeared to involve the suppression of mitogen-activated protein (MAP) kinase pathway. These findings are the first to suggest that, in rat cerebrocortical nerve terminals, resveratrol effects a decrease in MAP kinase activation, which subsequently suppresses voltage-dependent Ca(2+) channel activity and in so doing inhibits evoked glutamate release.
Chang
Yi
Y
School of Medicine, Fu Jen Catholic University, 510 Chung-Cheng Rd., Hsin-Chuang, Taipei Hsien 24205, Taiwan.
Wang
Su-Jane
SJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors
D000975:Antioxidants; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D026902:Potassium Channel Blockers; D013267:Stilbenes; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D015761:4-Aminopyridine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol; D002118:Calcium