INHIBITION OF HIGH-AFFINITY L-GLUTAMIC ACID UPTAKE INTO RAT CORTICAL SYNAPTOSOMES BY THE CONFORMATIONALLY RESTRICTED ANALOG OF GLUTAMIC-ACID, CIS-1-AMINOCYCLOBUTANE-1,3-DICARBOXYLIC ACID

被引：29

作者：

FLETCHER, EJ ^{[1
]}

MEWETT, KN ^{[1
]}

DREW, CA ^{[1
]}

ALLAN, RD ^{[1
]}

JOHNSTON, GAR ^{[1
]}

机构：

[1] UNIV SYDNEY,DEPT PHARMACOL,SYDNEY,NSW 2006,AUSTRALIA

来源：

NEUROSCIENCE LETTERS | 1991年 / 121卷 / 1-2期

关键词：

GLUTAMIC ACID; UPTAKE INHIBITION; CYCLOBUTANE DERIVATIVE;

D O I：

10.1016/0304-3940(91)90667-I

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The action of two cyclobutane derivatives of L-glutamic acid on the high affinity uptake of L-glutamic acid was investigated using a preparation of synaptosomes from rat cerebral cortex. cis-1-Aminocyclobutane-1,3-dicarboxylic acid (also known as trans-2,4-methanoglutamic acid) potently inhibited L-glutamic acid uptake (IC50 30 mu-M), whereas trans-1-aminocyclobutane-1,3-dicarboxylic acid (also known as cis-2,4-methanoglutamic acid), a potent N-methyl-D-aspartate (NMDA) agonist, was inactive. Analysis of the kinetics of L-glutamic acid uptake in the presence and absence of cis-1-aminocyclobutane-1,3-dicarboxylic acid (CACB) suggests that it may act as a competitive inhibitor (K(i) 8 mu-M). CACB may be substrate for the L-glutamic acid high-affinity uptake carrier since preincubation of CACB with the synaptosomal preparation increased its potency in inhibiting L-glutamic acid uptake. The conformationally restricted structure of CACB may be indicative of the conformations of L-glutamic acid that interact with the high affinity uptake carrier.

引用

页码：133 / 135

页数：3

共 15 条

[1]

ALLAN RD, IN PRESS J MED CHEM

[2] STEREOSPECIFICITY OF INHIBITION OF L-GLUTAMATE AND L-ASPARTATE HIGH AFFINITY UPTAKE IN RAT-BRAIN SLICES BY THREO-3-HYDROXYASPARTATE [J].