MODULATION OF GABA-A AND GLYCINE RECEPTORS BY CHLORMETHIAZOLE

被引:57
作者
HALES, TG [1 ]
LAMBERT, JJ [1 ]
机构
[1] UNIV DUNDEE,NINEWELLS HOSP & MED SCH,DEPT PHARMACOL & CLIN PHARMACOL,NEUROSCI RES GRP,DUNDEE DD1 9SY,SCOTLAND
关键词
CHLORMETHIAZOLE; GABA-A RECEPTORS; GLYCINE RECEPTORS; PATCH-CLAMP; ANESTHETICS (GENERAL); ANTICONVULSANTS;
D O I
10.1016/0014-2999(92)90410-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The influence of chlormethiazole, on currents evoked by gamma-aminobutyric acid (GABA) and glycine, was investigated under voltage-clamp conditions, in bovine chromaffin cells and murine spinal neurones, respectively. Chlormethiazole (30 and 100-mu-M) dose dependently potentiated currents activated by either inhibitory neurotransmitter. The potentiation of the GABA-evoked response occurred without altering the reversal potential and was not influenced by the benzodiazepine receptor antagonist Ro 15-1788 (300 nM). GABA-gated channels, recorded from outside-out membrane patches, showed increased probability of being in the conducting state in the presence of chlormethiazole. High concentrations of chlormethiazole (3 mM) activated bicuculline (1-mu-M)-sensitive whole-cell currents with a reversal potential similar to the chloride equilibrium potential. Chlormethiazole potentiates GABA- and glycine-activated currents and at higher doses, directly activates the GABA(A) receptor.
引用
收藏
页码:239 / 246
页数:8
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