BIOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF SIGMA RECEPTORS

Sigma 受体的生物学和生化特征

• 批准号: 5201685
• 负责人: T P SU
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201685
• 关键词: PCP receptor; affinity chromatography; biochemistry; dizocilpine; drug addiction antagonist; drug receptors; laboratory rat; learning; ligands; mecamylamine; memory; nimodipine; protein purification; psychological tests; psychopharmacology; receptor binding

This project delineates biochemical and pharmacological properties of sigma receptors and ligands. Sigma receptors are found to modulate in an agonist-antagonist fashion learning and memory impairments induced by drugs acting as antagonists at least three different receptor systems: mecamylamine (the nicotinic acetylcholine receptor), MK-801 (the NMDA/PCP receptor), and nimodipine (the L-type calcium channel). Learning capacities are evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, and the step-down passive avoidance and the water-maze test for long-term memory. PRE-084, a selective sigma ligand discovered at this laboratory, attenuate mecamylamine, MK-801, and nimodipine-induced impairment of memory processes in all three tests. These effects of PRE-084 are antagonized by a sigma receptor antagonist BMY-14802. Utilizing a new sigma receptor ligand synthesized in this laboratory, DAPE (N-(2-[3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)- (2-[1-pyrrolidinyl])ethylamine), sigma receptors solubilized from rat liver membranes are purified to nearly 2,000-fold via an affinity chromatography. Further purification of the sigma receptors is underway.

该项目描述的生化和药理学性质