Acute, chronic and differential effects of several anesthetic barbiturates on glutamate receptor activation in neuronal culture.
Acute, chronic and differential effects of several anesthetic barbiturates on glutamate receptor activation in neuronal culture.
复制标题
几种麻醉巴比妥类药物对神经元培养物中谷氨酸受体激活的急性、慢性和差异性影响。
DOI：
10.1016/0006-8993(93)90501-d
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
McCaslin,PP
中科院分区：
文献类型：
--
作者：
Cai,Z;McCaslin,PP
在神经元组织培养中研究了几种麻醉剂巴比妥类药物（治疗浓度）对兴奋性氨基酸（EAA）诱导的细胞内钙水平（[Ca 2 +]i）升高的急性和慢性影响。超短效巴比妥酸盐，thiamylal，是有效的阻断升高[Ca 2 +] i诱导红藻氨酸，N-甲基-d-天冬氨酸（NMDA），和quisqualate或膜去极化与40 mM KCl。结构相似的巴比妥酸盐，司可巴比妥，其与硫代戊醛的不同之处仅在于用氧代替硫，能够阻断由上述EAA诱导的升高，但效果不如硫代戊醛，并且没有显著降低由KCl引起的膜去极化引起的[Ca 2 +] i。戊巴比妥，而不同的司可巴比妥只有一个甲基，是没有影响的NMDA-或40 mM KCl-诱导的[Ca 2 +]i的升高。相反，赛庚啶，一种已被证明能阻断Ca 2+通道的化合物，与上述巴比妥类药物具有不同的特性，因为赛庚啶在阻断KCl引起的膜去极化引起的[Ca 2 +]i升高方面更有效，而巴比妥类药物在降低EAA引起的[Ca 2 +] i方面更有效。抗惊厥药巴比妥酸盐，苯巴比妥，并没有减少升高的[Ca 2 +] i诱导的任何EAA测试或与KCl的膜去极化。当细胞用硫代戊醛慢性处理4天时，突然停药后2-6小时，对红藻氨酸和NMDA诱导的[Ca ~（2+）] i升高有高反应性，而对使君子酸无反应。苯巴比妥长期治疗后未观察到类似的高反应性。总的来说，这些结果表明，硫代戊醛的长期给药影响与急性给药受影响的类似途径，并且巴比妥酸盐侧链的轻微结构变化导致阻断EAA和KCl诱导的[Ca 2 +]i升高的非常显著的差异。
The acute and chronic effects of several anesthetic barbiturates, in therapeutic concentrations, on the excitatory amino acid (EAA)-induced elevation of intracellular calcium levels ([Ca2+]i) were examined in neuronal tissue culture. The ultrashort-acting barbiturate, thiamylal, was effective in blocking elevations of [Ca2+]iinduced by kainate,N-methyl-d-aspartate (NMDA), and quisqualate or by membrane depolarization with 40 mM KCl. The structurally similar barbiturate, secobarbital which differs from thiamylal only by having an oxygen in place of a sulfur, was able to block elevations induced by the above EAAs but was less effective than thiamylal and did not significantly reduce [Ca2+]ithat resulted from membrane depolarization with KCl. Pentobarbital, while differing from secobarbital by only a methyl group, was without effect on either the NMDA- or 40 mM KCl-induced elevations of [Ca2+]i. By contrast, cyproheptadine, a compound that has been shown to block Ca2+channels, has a different profile from the above barbiturates in that cyproheptadine is more effective in blocking elevation of [Ca2+]i, induced by membrane depolarization with KCl while the barbiturates are more effective in reducing [Ca2+]iinduced by EAAs. An anticonvulsant barbiturate, phenobarbital, did not reduced elevations of [Ca2+]iinduced by any EAA tested or by membrane depolarization with KCl. When cells were treated chronically with thiamylal for 4 days, 2–6 h after the abrupt drug withdrawal there was a hyperresponsiveness to the elevations of [Ca2+]iinduced by both kainate and NMDA but not by quisqualate. A similar hyperresponsiveness was not seen after the chronic treatment with phenobarbital. Collectively, these results show that the chronic administration of thiamylal affects similar pathways that are affected with the acute drug administration, and also that slight structural changes in the barbiturate side chains result in very significant differences in blocking EAA- and KCl-induced elevations of [Ca2+]i.