백서 대뇌피질절편의 허혈유사조건에 의한
[3H]GABA유리의 특성 |
송대원, 김영현,김기원 |
지방공사 남원의료원 신경과 ·전북대학교 의과대학 신경과학교실*, 약리학교실** |
Characteristics of [3H]GABA release evoked by oxygen-glucose deprivation in rat cerebral cortex slices |
Dae-Won Song, M.D., · Young-Hyun Kim*, M.D., · Ki-Won Kim**, M.D. |
Department of Neurology, Namwon Province Medical Center, Department of Neurology* and Pharmacology**, Medical school, Chonbuk National University |
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Abstract |
In present study, the mechanism for oxygen-glucose deprivation -induced [3H]γ-aminobutyric acid (GABA) from cerebral cortex slices of the rat was examined. Deprivation of oxygen and glucose(OGD) from Mg2+-free artificial cerebrospinal fluid, induced significant release of [3H]GABA (7.4±0.6% of total tissue content) from cerebral cortex slices.
OGD-induced release of [3H]GABA was significantly attenuated by tetrodotoxin(TTX)(1 μM), Mg2+(1.2 mM), MK-801(10 μM), ketamine(10 μM), N-methyl-D-aspartate(NMDA) receptor antagonists, (DNQX)(30 μM), and 6-cyano-7-nitroquinoxaline-2,3-dione(CNQX)(30 μM), kainate/AMPA receptor antagonists, or 6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2, 3-dione(NBQX)(10 μM), a selective AMPA receptor blocker. OGD-evoked [3H]GABA release was attenuated by (NG-nitro-L-arginine methyl ester(L-NAME) and 7-nitronidazole, nitric oxide synthase inhibitors, and methylene blue, potentiated by zaprinast, a cGMP phosphodiesterase inhibitor. OGD-induced release of [3H]GABA was inhibited by nipecotic acid, a selective neuronal GABA transporter blocker, and potentiated by DL-2.4-diamino-n-butyric acid(DABA), a neuronal and glial GABA transporter blocker. Dantrolene (30 μM) and 1,2-bis (2-aminophenoxy)-ethane-N, N, N', N'-tetraacetic acid tetrakis (acetoxymethyl) ester(BAPTA-AM)(30 μM), inhibitors of intracellular Ca2+ release, verapamil(5 μM), ω-conotoxinGVIA(100 nM) and ω-agatoxinIVA(100 nM), inhibitors of voltage-dependent Ca2+ channels, significantly attenuated the OGD-induced release of [3H]GABA.
These results suggest that glutamate is involved in OGD-evoked [3H]GABA release, and this release is achieved by Ca2+-dependent exocytosis and reversal of transporters, and can be modulated by various neuronal mechanisms.
Key Words : Oxygen-glucose deprivation, GABA release, Glgutamate |
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