NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

精神药物的神经化学作用

• 批准号: 3374738
• 负责人: SOLOMON H. SNYDER
• 金额: $ 39.38万
• 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/3374738
• 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.

这笔赠款用于与以下项目有关的几个项目 神经递质受体，参与神经递质的酶 性情与药物相互作用。对三个方面进行了详细的描述。 一种是研究佛波酯受体，这种受体似乎与 蛋白激酶C的实验方法被提出来确定一个角色 蛋白激酶C在突触传递中的作用。将使用佛波酯 作为修饰神经递质对平滑肌和血管的影响的探针 来研究锂的作用。佛波醇酯的影响将被探索。 神经递质释放时。放射自显影与免疫细胞化学 佛波酯受体的本地化也将进行。一秒钟 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诱导了一种 帕金森氏症的实验性形式。详细的放射自显影地图 将获得MPTP受体结合位点数。中的应变差异 将探索MPTP的处理方式，以寻找与压力的相关性 MPTP的神经毒性差异。MPTP绑定的关系 单胺氧化酶的位置将被检查。第三个项目涉及 钙拮抗剂受体。不同的受体结合部位 地尔硫、维拉帕米类药物和二氢吡啶类药物将被表征 并探索它们之间的相互关系。钙拮抗剂对血管内皮细胞生长的影响 将检测突触体钙流量和钙之间的相互作用 将对不同类别的钙离子通量拮抗剂进行评估。一个 腺苷环化酶与突触体钙通量的关系也将是 检查过了。