CHARACTERIZATION OF RECEPTORS FOR FMRFAMIDE-RELATED NEUROPEPTIDES

FMRF酰胺相关神经肽受体的表征

• 批准号: 3857155
• 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/3857155
• 关键词: Cephalopoda; G protein; adenylate cyclase; animal tissue; central nervous system; dynorphins; laboratory rat; ligands; naloxone; narcotic antagonists; neuropeptide receptor; neuropeptides; oxytocin; potassium; protein structure function; vasopressins

This project aimed to characterize the receptors for Phe-Met-Arg-Phe-NH2, (FMRFamide) and Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, in molluscan and mammalian CNS, respectively. The FMRFamide receptors in squid optic lobe were determined to be coupled to stimulation of adenylate cyclase through a membrane G-protein, and had ligand binding preferences similar to those in Helix aspersa. Radioactive photoaffinity ligands were used to label the optic lobe FMRFamide receptor, which appears to be a 52,000 MW protein that can be solubilized by Triton X-100. Adenylate cyclase activity of rat spinal cord membranes was unaffected by NPFF, whereas kappa opioid dynorphins weakly inhibited AC activity. In 1 of 2 experiments on isolated terminals of rat neural lobe, dynorphin A 1-8 inhibited vasopressin and oxytocin secretion stimulated by high potassium, and this inhibition was reversed by NPFF or naloxone. A putative NPFF antagonist (daY8Ra) attenuated the NPFF-induced opiate abstinence syndrome in naive rats. High dosage, however, caused NPFF-like abstinence symptoms. Interestingly, daY8Ra also blocked the naloxone-induced withdrawal symptoms in morphine-dependent rats, suggesting that NPFF is involved in the expression of withdrawal syndrome in both normal and dependent rats.

该项目旨在表征Phe-Met-Arg-Phe-NH 2的受体， （FMRFamide）和Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH 2，在软体动物中， 哺乳动物CNS。 鱿鱼视叶的FMRFamide受体 被确定为与腺苷酸环化酶的刺激偶联， 一种膜G蛋白，并具有类似于那些 在Hataspersa。 放射性光亲和配体用于标记 视叶FMRFamide受体，似乎是一种52，000 MW的蛋白质， 可被Triton X-100增溶。 大鼠腺苷酸环化酶活性 脊髓膜不受NPFF的影响，而κ阿片样物质 强啡肽对AC活性有弱的抑制作用。 在2项实验中的1项中， 强啡肽A1 -8抑制加压素和 高钾刺激催产素分泌，这种抑制作用是 NPFF或纳洛酮逆转。 一种推定的NPFF拮抗剂（daY 8 Ra） 减轻NPFF诱导的未处理大鼠阿片戒断综合征。 高 然而，剂量引起NPFF样戒断症状。有趣的是， daY 8 Ra也阻断了纳洛酮诱导的戒断症状。 吗啡依赖大鼠，表明NPFF参与表达 戒断综合征的发生率。