CHARACTERIZATION OF RECEPTORS FOR FMRFAMIDE-RELATED NEUROPEPTIDES

FMRF酰胺相关神经肽受体的表征

• 批准号: 3842358
• 负责人: G J CHIN
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 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/3842358
• 关键词: Cephalopoda; G protein; adenylate cyclase; animal tissue; central nervous system; ligands; molecular size; neuropeptide receptor; neuropeptides; oxytocin; protein structure function; receptor coupling

This project is concerned with the identification and characterization of the receptor for FMRFamide (Phe-Met-Arg-Phe-NH2), a widely distributed neuropeptide. FMRFamine receptors were solubilized from squid brain using the zwitterionic detergent CHAPS. The solubilized receptor bound FMRFamide with Kd about 0.15 Nm and displayed a structure-activity relationship similar to that of the receptor in unsolubilized squid membranes. Ligand affinity was sensitive to guanine nucleotides, indicating the coupling of the receptor to a G protein- regulated pathway and consistent with earlier work demonstrating the stimulation of squid adenylate cyclase by FMRFamide. Current efforts are directed towards obtaining an estimate of the molecular size of the receptor. An earlier approach using photoreactive analogues of FMRFaminde identified a protein of 52 kDa, but subsequent work suggested that this protein is not the receptor on the basis of differences in ligand specificity and affinity, and GTP sensitivity. This protein may be an enzyme involved in peptide processing because of its specificity for FMRFamide in comparison to the non-amidated FMRF.

这个项目涉及到鉴定和表征 一种广谱的FMRFamide受体(Phe-Met-Arg-Phe-NH2) 分布神经肽。FMR饥荒受体是从 鱿鱼脑使用两性离子洗涤剂CHAPS。增溶的 受体与FMRFamide结合，Kd约为0.15 Nm，并显示 与受体相似的构效关系 未增溶的鱿鱼膜。配基亲和力对鸟嘌呤敏感 核苷酸，表明受体与G蛋白偶联- 受调控的途径，并与早期证明的工作一致 FMRFamide对鱿鱼腺苷环化酶的刺激作用。目前的努力是 旨在获得对分子大小的估计 受体。使用光反应类似物的早期方法 FMRFaminde发现了一种52 kDa的蛋白质，但随后的研究表明 这种蛋白质不是受体，这是基于 配体的特异性和亲和力，以及GTP的敏感性。这种蛋白质可能 是一种参与多肽加工的酶，因为它的专一性 与未经胺化的FMRF相比，FMRFamide。