CHARACTERIZATION OF RECEPTORS FOR FMRFAMIDE-RELATED NEUROPEPTIDES

本项目旨在鉴定Phe-Met-Arg-Phe-NH_2受体， (FMRFamide)和Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 哺乳动物中枢神经系统。鱿鱼视叶中的FMRFamide受体 被确定为与腺苷环化酶的刺激偶联 一种膜G蛋白，其配体结合偏好类似于 在螺旋藻中。放射性光亲和配体被用来标记 视叶FMRFamide受体，它似乎是一个52,000 mW的蛋白质， 可被Triton X-100增溶。大鼠腺苷酸环化酶活力的研究 NPFF对脊髓膜无影响，而kappa阿片类药物 强啡肽对AC活性有微弱的抑制作用。在2个实验中的1个中， 大鼠神经叶终末强啡肽A1-8抑制后叶加压素和 高钾刺激催产素分泌，这种抑制作用 被NPFF或纳洛酮逆转。一个可能的NPFF拮抗剂(DaY8ra) 减轻NPFF诱导的幼年大鼠阿片类戒断综合征。高 然而，剂量会引起类似NPFF的戒断症状。有趣的是， DaY8Ra还阻断了纳洛酮诱导的戒断症状。 吗啡依赖大鼠，提示NPFF参与该基因的表达 对正常大鼠和依赖大鼠的戒断综合症的影响。

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.