GAMMA-VINYL GABA (4-AMINO-HEX-5-ENOIC ACID), A NEW SELECTIVE IRREVERSIBLE INHIBITOR OF GABA-T - EFFECTS ON BRAIN GABA METABOLISM IN MICE
GAMMA-VINYL GABA (4-AMINO-HEX-5-ENOIC ACID), A NEW SELECTIVE IRREVERSIBLE INHIBITOR OF GABA-T - EFFECTS ON BRAIN GABA METABOLISM IN MICE
复制标题
DOI：
10.1111/j.1471-4159.1977.tb10721.x
复制
发表时间：
1977-01-01
影响因子：
4.7
通讯作者：
SCHECHTER, PJ
中科院分区：
文献类型：
--
作者：
JUNG, MJ;LIPPERT, B;SCHECHTER, PJ
可以利用。-乙烯基GABA（4-氨基己烯酸，RMI 71754）是GABA- t的体外催化抑制剂。当通过外周途径给药给小鼠时，它穿过血脑屏障，诱导持久的、剂量依赖性的、不可逆的脑GABA转氨酶（GABA- t）抑制。谷氨酸脱羧酶（GAD）即使在最高剂量下也只受到轻微影响。-乙烯基GABA对脑内琥珀酸半醛脱氢酶、天冬氨酸转氨酶和丙氨酸转氨酶活性影响不大或无影响。GABA- t抑制伴随着持续的脑GABA浓度的剂量依赖性增加。从GABA的积累速率估计GABA在脑内的周转量至少为6.5 μ。根据酶活性的恢复，GABA-T的半衰期为3.4天，GAD的半衰期约为2.4天。-乙烯基GABA对脑GABA代谢的操纵应该是有价值的。
.gamma.-Vinyl GABA (4-amino-hex-5-enoic acid, RMI 71754) is a catalytic inhibitor of GABA-T in vitro. When given by a peripheral route to mice, it crossed the blood-brain barrier and induced a long-lasting, dose-dependent, irreversible inhibition of brain GABA transaminase (GABA-T). Glutamate decarboxylase (GAD) was only slightly affected even at the highest doses used. .gamma.-Vinyl GABA had little or no effect on brain succinate semialdehyde dehydrogenase, aspartate transaminase and alanine transaminase activities. GABA-T inhibition was accompanied by a sustained dose-dependent increase of brain GABA concentration. From the rate of accumulation of GABA it was estimated that GABA turnover in brain was at least 6.5 .mu.mol/g per h. Based on recovery of enzyme activity the half-life of GABA-T was 3.4 days, that of GAD was about 2.4 days. .gamma.-Vinyl GABA should be valuable for manipulations of brain GABA metabolism.