神经毒素α-氨基己二酸对大鼠纹状体中谷氨酸转运体和胶质酶的抑制作用。
Inhibition of the glutamate transporter and glial enzymes in rat striatum by the gliotoxin, alpha aminoadipate.
作者信息
McBean G J
机构信息
Department of Biochemistry, University College, Belfield, Dublin, Ireland.
出版信息
Br J Pharmacol. 1994 Oct;113(2):536-40. doi: 10.1111/j.1476-5381.1994.tb17022.x.
Abstract
- The effect of the gliotoxic analogue of glutamate, alpha aminoadipate, on the high affinity transport of D-[3H]-aspartate into a crude striatal P2 preparation, and on the activity of two enzymes of which glutamate is the substrate has been examined. 2. The L-isomer of alpha aminoadipate competitively inhibited the transport protein, with a Ki value of 192 microM, whereas the D-isomer of alpha aminoadipate was ineffective. The potent convulsant, L-methionine-S-sulphoximine, was also without effect on the activity of the glutamate transport protein. 3. L-alpha Aminoadipate was a competitive inhibitor of both glutamine synthetase, and gamma-glutamylcysteine synthetase, with Ki values of 209 microM and 7 mM respectively. Once again, the D-isomer of alpha aminoadipate was a far weaker inhibitor of either enzyme. 4. The results are discussed in terms of the mechanism of action of alpha aminoadipate in causing toxicity of glial cells.
摘要
- 已研究了谷氨酸的神经毒性类似物α-氨基己二酸对D-[3H]-天冬氨酸向粗纹状体P2制剂中的高亲和力转运以及对以谷氨酸为底物的两种酶活性的影响。2. α-氨基己二酸的L-异构体竞争性抑制转运蛋白，其Ki值为192微摩尔，而α-氨基己二酸的D-异构体则无作用。强效惊厥剂L-蛋氨酸-S-亚砜亚胺对谷氨酸转运蛋白的活性也无影响。3. L-α-氨基己二酸是谷氨酰胺合成酶和γ-谷氨酰半胱氨酸合成酶的竞争性抑制剂，其Ki值分别为209微摩尔和7毫摩尔。同样，α-氨基己二酸的D-异构体对这两种酶的抑制作用要弱得多。4. 根据α-氨基己二酸导致神经胶质细胞毒性的作用机制对结果进行了讨论。
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