Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor-mediated calcium flux in brain membrane vesicles.
Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor-mediated calcium flux in brain membrane vesicles.
复制标题
麻醉剂和惊厥巴比妥类药物对 N-甲基-D-天冬氨酸受体介导的脑膜囊泡钙通量的影响。
DOI：
10.1159/000139246
复制
发表时间：
1994
期刊：
影响因子：
3.1
通讯作者：
Daniell,LC
中科院分区：
文献类型：
--
作者：
Daniell,LC
在小鼠海马无细胞膜囊泡制备中，研究了麻醉剂和惊厥剂巴比妥类药物对脑N-甲基-D-天冬氨酸（NMDA）受体功能的影响。在用NMDA受体激动剂L-谷氨酸盐刺激后，使用荧光染料Indo-1测定细胞内游离钙浓度（Cai）的增加。麻醉剂巴比妥酸盐以浓度依赖性方式抑制NMDA反应，其效力顺序为司可巴比妥>异戊巴比妥>戊巴比妥>甲氧巴比妥=苯巴比妥>>巴比妥。然而，这些巴比妥类药物的IC 50值大于可能的血液麻醉剂浓度。在小鼠中具有麻醉和惊厥作用的巴比妥类药物[戊巴比妥和司可巴比妥的光学异构体，5-（2-亚环己基乙基）-5-乙基巴比妥酸和（+/-）-二甲基丁基巴比妥酸]也可降低NMDA反应。外消旋戊巴比妥或戊巴比妥异构体对NMDA反应的抑制是非竞争性的。休息蔡被改变的所有巴比妥类药物测试，除了司可巴比妥和巴比妥，但不是以一致的方式，这表明巴比妥类药物对休息蔡的影响不相关的NMDA受体反应的影响，或他们的行为影响。这些结果表明，麻醉和惊厥巴比妥类药物抑制NMDA反应，但它们的麻醉和惊厥活性可能主要是由于它们对其他脑靶点的作用。
The effects of anesthetic and convulsant barbiturates on brain N-methyl-D-aspartate (NMDA) receptor function were examined in a cell-free membrane vesicle preparation from mouse hippocampus. Increases in intracellular free calcium concentrations (Cai) were determined using a fluorescent dye, Indo-1 after stimulation with the NMDA receptor agonist, L-glutamate. Anesthetic barbiturates inhibited NMDA responses in a concentration-dependent manner with a rank order of potency of secobarbital > amobarbital > pentobarbital > mephobarbital = Phenobarbital >> barbital. However, the IC50 values for these barbiturates were larger than probable blood anesthetic concentrations. Barbiturates with both anesthetic and convulsant effects in mice [optical isomers of pentobarbital and secobarbital, 5-(2-cyclohexylideneethyl)-5-ethylbarbituric acid and (+/–)-dimethylbutylbarbituric acid] also reduced NMDA responses. Inhibition of NMDA responses by racemic pentobarbital or isomers of pentobarbital was noncompetitive. Resting Cai was altered by all barbiturates tested except secobarbital and barbital, but not in a consistent manner, suggesting that the effect of barbiturates on resting Caiis not related either to their effects on NMDA receptor responses or to their behavioral effects. Therse results show that anesthetic and convulsant barbiturates inhibit NMDA responses, but their anesthetic and convulsant activities may be primarily due to their effects on other brain targets.