Zuiderwijk M, Veenstra E, Lopes da Silva F H, Ghijsen W E
Graduate School for the Neurosciences, University of Amsterdam, Netherlands.
Eur J Pharmacol. 1996 Jul 4;307(3):275-82. doi: 10.1016/0014-2999(96)00284-1.
This report describes the in vivo effects of the uptake carrier blockers 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid hydrochloride (SK & F 89976-A) and L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC) on basal and K(+)-evoked extracellular levels of gamma-aminobutyric acid (GABA), glutamate, aspartate and taurine in the hippocampus of anaesthetised rats, using the microdialysis technique. SK & F 89976-A increased extracellular GABA levels under K(+)-depolarised conditions and did not affect extracellular glutamate, aspartate and taurine levels, indicating its selective effect on GABA uptake L-trans-PDC dose dependently increased basal and K(+)-evoked extracellular glutamate levels, and did not affect extracellular GABA levels, but increased basal aspartate and taurine levels. The K(+)-evoked release of GABA and glutamate, measured in the presence of both SK & F 89976-A and L-trans-PDC, was Ca(2+)-dependent for about 50% and 65%, respectively. In contrast, the release of the putative amino acid transmitters aspartate and taurine was not Ca(2+)-dependent. These results indicate that (1) in rat hippocampus uptake carriers actively regulate extracellular GABA and glutamate levels, (2) the GABA and glutamate released by K+ was derived from both Ca(2+)-dependent (presumably vesicular) and Ca(2+)-independent (presumably cytosolic) pools, whereas aspartate and taurine release was exclusively from Ca(2+)-independent pools.
本报告运用微透析技术，描述了摄取载体阻滞剂盐酸1-(4,4-二苯基-3-丁烯基)-3-哌啶羧酸（SK & F 89976-A）和L-反式脯氨酸-2,4-二羧酸（L-反式-PDC）对麻醉大鼠海马中γ-氨基丁酸（GABA）、谷氨酸、天冬氨酸和牛磺酸基础水平及钾离子诱发的细胞外水平的体内影响。SK & F 89976-A在钾离子去极化条件下增加细胞外GABA水平，且不影响细胞外谷氨酸、天冬氨酸和牛磺酸水平，表明其对GABA摄取具有选择性作用。L-反式-PDC剂量依赖性地增加基础及钾离子诱发的细胞外谷氨酸水平，不影响细胞外GABA水平，但增加基础天冬氨酸和牛磺酸水平。在同时存在SK & F 89976-A和L-反式-PDC的情况下测得的钾离子诱发的GABA和谷氨酸释放，分别约50%和65%依赖于钙离子。相反，假定的氨基酸递质天冬氨酸和牛磺酸的释放不依赖于钙离子。这些结果表明：（1）在大鼠海马中，摄取载体积极调节细胞外GABA和谷氨酸水平；（2）钾离子释放的GABA和谷氨酸来源于钙离子依赖性（可能是囊泡性）和非钙离子依赖性（可能是胞浆性）池，而天冬氨酸和牛磺酸的释放仅来自非钙离子依赖性池。
