ACUTE & CHRONIC BARBITURATES: IN VITRO BIOCHEMISTRY

这个实验室和其他实验室都有明确的证据表明 巴比妥酸盐与兴奋性氨基酸(EAA)神经递质相互作用。 然而，目前还不清楚巴比妥酸盐在哪里影响这些 发射机。他们很可能不会直接对地产代理监管局采取行动 受体，而不是影响受体介导的事件。这项提议将 检验巴比妥类药物的急性和慢性作用于 EAA和钾诱导的~(45)Ca~(++)内流和细胞周期升高 鸟苷一磷酸(CGMP)与钙的相互作用是次要的 与EAA受体、神经元去极化相关的通道 和/或神经递质的突触前释放。的原生文化 小脑颗粒神经元是研究兴奋性的极佳系统 氨基酸(EAA)受体。此外，在初步结果中， 本提案我提供的数据表明，本系统也是一款优秀的 系统，以研究巴比妥酸盐的影响。戊巴比妥可预防 EAA可引起这些神经元cGMP和45Ca+内流的增加。在……里面 此外，将这些神经元暴露在戊巴比妥中几天的结果 对EAA诱导的cGMP和45Ca++升高的高反应性 在戊巴比妥从培养基中去除后流入。 这项建议的主要目标是审查通过哪些机制 巴比妥酸盐通过集中于 巴比妥酸盐与EAA受体内衬的钙通道。的直接影响 将使用cGMP检测几种巴比妥酸盐对钙通道的影响 以升高、45Ca+内流和谷氨酸释放为参数 紧随其后。设计的实验将分离出 巴比妥类药物对EAA和钙通道的影响 在GABA受体和氯离子通道上。

There is clear evidence from both this and other laboratories showing that barbiturates interact with excitatory amino acid (EAA) neurotransmitters. It is unclear, however, where barbiturates are acting to affect these transmitters. It is probable that they do not directly act on EAA receptors but rather affect receptor-mediated events. This proposal will test the hypothesis that the acute and chronic actions of barbiturates on the EAA-and potassium-induced influx of 45Ca++ and the elevation of cyclic guanosine monophosphate (cGMP) are secondary to an interaction with calcium channels associated with either the EAA receptor, neuronal depolarization and/or the presynaptic release of neurotransmitter. Primary cultures of cerebellar granule neurons are an excellent system for studying excitatory amino acid (EAA) receptors. Furthermore, in the preliminary results of this proposal I provide data showing that this system is also an excellent system to study the effects of barbiturates. Pentobarbital prevents the EAA-induced elevation of both cGMP and 45Ca++ influx n these neurons. In addition, exposing these neurons to pentobarbital for several days results in a hyperresponsiveness to the EAA-induced elevation of cGMP and 45Ca++ influx after pentobarbital is removed from the culture media. The major objective of this proposal is to examine the mechanisms by which barbiturates exert the above actions by focusing on the interaction of barbiturates with EAA receptor-lined calcium channels. A direct effect of several barbiturates on calcium channels will be examined using cGMP elevation, 45Ca++ influx and the release of glutamate as parameters to be followed. Experiments are designed which will separate the effects of barbiturates on EAA and calcium channels from the effects of barbiturates on the GABA receptor and chloride channels.