ACUTE & CHRONIC BARBITURATES: IN VITRO BIOCHEMISTRY

该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类药物在何处影响这些 发射器 他们很可能不会直接对监管局采取行动 受体，而是影响受体介导的事件。 这项建议会 检验巴比妥类药物的急性和慢性作用对 EAA和钾诱导的~（45）Ca ~（++）内流和循环功能的升高 鸟苷酸（cGMP）是次要的相互作用与钙 与EAA受体、神经元去极化 和/或神经递质的突触前释放。 的原代培养物 小脑颗粒神经元是一个很好的研究兴奋性的系统， 氨基酸（EAA）受体。 此外，在初步结果中， 这个建议我提供的数据表明，这个系统也是一个很好的 系统来研究巴比妥类药物的作用。 戊巴比妥可防止 EAA引起cGMP和~（45）Ca ~（++）内流增加。 在 此外，将这些神经元暴露于戊巴比妥几天， 对EAA诱导的cGMP和45 Ca ++升高的高反应性 从培养基中除去戊巴比妥后流入。 这项建议的主要目的是审查机制， 巴比妥类药物通过关注以下物质的相互作用发挥上述作用： 巴比妥类药物与EAA受体内衬钙通道。 的直接作用 将使用cGMP检查几种巴比妥酸盐对钙通道的作用 升高，45 Ca ++内流和谷氨酸的释放作为参数， 跟踪了 实验设计将分离的影响， 从巴比妥类药物对EAA和钙通道的影响看巴比妥类药物对EAA和钙通道的作用 对GABA受体和氯离子通道的影响

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.