NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

精神药物的神经化学作用

• 批准号: 3374737
• 负责人: SOLOMON H. SNYDER
• 金额: $ 39.02万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3374737
• 关键词: Parkinson's disease; autoradiography; brain mapping; calcium channel blockers; calcium flux; calcium metabolism; cyclic AMP; drug metabolism; drug receptors; electron microscopy; guinea pigs; histochemistry /cytochemistry; immunochemistry; laboratory rat; lithium; monoclonal antibody; neurochemistry; neuropharmacology; neurotoxins; neurotransmitter metabolism; neurotransmitter receptor; phorbols; protein kinase C; psychobiology; smooth muscle; synaptosomes; tritium

This grant is addressed toward several projects relating to neurotransmitter receptors, enzymes involved in neurotransmitter disposition and drug interactions. Three areas are described in detail. One deals with phorbol ester receptors which appear to be identical with protein kinase C. Experimental approaches are proposed to identify a role of protein kinase C in synaptic transmission. Phorbol esters will be used as probes to modify the effects of neurotransmitters upon smooth muscle and to examine the role of lithium. Effects of phorbol esters will be explored upon neurotransmitter release. Autoradiographic and immunocytochemical localization of phorbol ester receptors will also be carried out. A second project deals with the actions of the neurotoxin MPTP (1-mythyl-4-phenyl-1,2,3,6,tetrayhydropyridine). MPTP induces an experimental form of Parkinson's Disease. Detailed autoradiographic maps of MPTP receptor binding sites will be obtained. Strain differences in MPTP disposition will be explored to look for correlations with strain differences in the neurotoxicity of MPTP. The relationship of MPTP binding sites to monoamine oxidase will be examined. A third project deals with calcium antagonist receptors. Different receptor binding sites for diltiazem, verapamil-like drugs and dihydropyridines will be characterized and their inter-relationships explored. Effects of calcium antagonists on synaptosomal calcium flux will be examined and interactions among calcium antagonists of different classes upon calcium flux will be evaluated. A relationship of adenylate cyclase to synaptosomal calcium flux will also be examined.

这笔赠款是针对几个项目有关， 神经递质受体，参与神经递质的酶 处置和药物相互作用。 三个方面进行了详细说明。 一个涉及佛波酯受体，其似乎与 蛋白激酶C 提出了实验方法来确定一个角色 蛋白激酶C在突触传递中的作用 佛波酯将被用于 作为探针来改变神经递质对平滑肌的作用， 来研究锂的作用 将探索佛波酯的影响 神经递质的释放。 放射自显影和免疫细胞化学 还将进行佛波醇酯受体的定位。 第二 该项目涉及神经毒素MPTP的作用 （1-甲基-4-苯基-1，2，3，6，四氢吡啶）。 MPTP诱导 帕金森氏症的实验形式。 详细放射自显影图 的MPTP受体结合位点。 菌株差异 将探索MPTP处置以寻找与应变的相关性 MPTP神经毒性的差异。 MPTP结合的关系 将检查单胺氧化酶的位点。 第三个项目涉及 钙拮抗剂受体 不同的受体结合位点 地尔硫卓、维拉帕米样药物和二氢吡啶类药物将被表征 以及它们之间的相互关系。 钙拮抗剂的作用 将检查突触体钙流，并检查钙离子之间的相互作用。 将评价不同种类的拮抗剂对钙通量的影响。 一 腺苷酸环化酶与突触体钙流的关系也将被 考察