Estevez A Y, Song D, Phillis J W, O'Regan M H
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Brain Res Bull. 2000 May 1;52(1):45-50. doi: 10.1016/s0361-9230(00)00236-7.
Amino acid release from the rat cerebral cortex was analyzed using an in vivo cortical cup perfusion model. Topical applications of ouabain or high extracellular K(+) were used to mimic two dimensions of ischemic conditions which promote cell swelling and amino acid release. Ouabain (30 microM) induced significant releases of taurine, gamma-aminobutyric acid (GABA), aspartate, glutamate and phosphoethanolamine. The anion channel blocker, 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS; 1 mM), inhibited ouabain-induced release of all these amino acids except for glutamate. Exposure to high extracellular K(+) (75 mM) induced a delayed rise in the levels of taurine in the superfusates and an immediate increase in GABA levels. There were no significant releases of other amino acids. The release of taurine and GABA was sensitive to the blocking of anion channels with DIDS. Both ouabain- and high K(+)-induced taurine release is likely to be mediated by DIDS sensitive anion channels. The extracellular accumulation of the other amino acids, where insensitive to DIDS, may be mediated by mechanisms other than swelling-induced anion channels.
利用体内皮质杯灌注模型分析大鼠大脑皮质中氨基酸的释放。使用哇巴因局部应用或高细胞外钾离子(K(+))来模拟促进细胞肿胀和氨基酸释放的缺血条件的两个维度。哇巴因(30微摩尔)诱导牛磺酸、γ-氨基丁酸(GABA)、天冬氨酸、谷氨酸和磷酸乙醇胺显著释放。阴离子通道阻滞剂4,4'-二异硫氰基芪-2,2'-二磺酸(DIDS;1毫摩尔)抑制哇巴因诱导的除谷氨酸外所有这些氨基酸的释放。暴露于高细胞外钾离子(75毫摩尔)会导致灌流液中牛磺酸水平延迟升高以及GABA水平立即增加。其他氨基酸没有显著释放。牛磺酸和GABA的释放对DIDS阻断阴离子通道敏感。哇巴因和高钾诱导的牛磺酸释放可能均由DIDS敏感的阴离子通道介导。对DIDS不敏感的其他氨基酸的细胞外积累可能由肿胀诱导的阴离子通道以外的机制介导。