title: Involvement of protein kinase C in glutamate release from cultured microglia.
abstract: Glutamate release from microglial cells may cause neuronal damage. To elucidate the mechanism of glutamate release, we examined the possible regulation by nitric oxide and protein kinase C. Cultured microglia prepared from the whole brains of newborn rats released glutamate by the stimulation with lipopolysaccharide (LPS) dose dependently. The time course study revealed that glutamate release showed a long lag time about 6 h after LPS stimulation, whereas about 3 h lag time was observed in LPS-induced NO production. An inhibitor for NO synthase, N(G)-nitro-L-arginine, could effectively inhibit the glutamate release. Glutamate release induced by LPS was enhanced by 1 nM phorbol myristate acetate (PMA). Furthermore, high concentrations of PMA (>10 nM) induced glutamate release even without LPS stimulation. Glutamate release stimulated either by 100 ng/ml LPS or 100 nM PMA was inhibited by staurosporine, and also by alpha-aminoadipate. These results provide insight into the pathways regulating microglial pathological activation by protein kinase C and may be a base for the protection against microglia-evoked neurotoxicity.
authors.affiliation: Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan. yoichi@vet.osakafu-u.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Miho
authors.initials: M
authors.lastname: Ohmaki
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D019335:Nitroarginine; D018698:Glutamic Acid; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate