MET-ENKEPHALIN-ARG-PHE AND PHE-MET-ARG-PHE-NH2 IN THE BRAIN AND SPINAL CORD

大脑和脊髓中的 MET-脑啡肽-ARG-PHE 和 PHE-MET-ARG-PHE-NH2

• 批准号: 4696406
• 负责人: H-Y T YANG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 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/4696406
• 关键词: affinity chromatography; analgesia; antiserum; bioassay; brain mapping; brain metabolism; chemical structure function; drug interactions; drug metabolism; immunochemistry; naloxone; neurochemistry; neuropharmacology; neurotransmitter biosynthesis; neurotransmitter metabolism; oligopeptides; peptide chemical synthesis; pituitary gland; radioimmunoassay; spinal cord

Previously, we have presented several lines of evidence suggesting that Phe-Met-Arg-Phe-NH2-like (FMRF-NH2-like) peptide(s) in mammalian CNS may have modulatory role in opiate antinociception. FMRF-NH2 was a neuropeptide of clam origin, however, presence of FMRF-NH2-like peptides, which are distinct from the tetrapeptide FMRF-NH2, in mammalian CNS is now well known. In order to further explore the possible role of endogenous FMRF-NH2-like immunoreactivity in opiate antinociception, we have decided to chemically characterize the mammalian FMRF-NH2 like peptides. Two novel peptides, which are immunoreactive to FMRF-NH2 antiserum, have been purified to homogeneity from bovine brain and their amino acids sequences determined. Furthermore, these two peptides (octapeptide and octadecapeptide) were synthesized and biological activities were tested in rats. Both peptides, when injected intraventricularly, were found to decrease tail flick latencies of rats. One of the peptides, octapeptide, was found to attenuate the analgesia induced by morphine significantly. The molecular mechanism underlying this antiopiate effect of the novel mammalian FMRF-NH2 like peptide is under current investigation.

在此之前，我们已经提出了几条证据， 哺乳动物CNS中的Phe-Met-Arg-Phe-NH 2样（FMRF-NH 2样）肽可 在阿片类药物的镇痛作用中具有调节作用。 FMRF-NH 2是一种 然而，蛤类来源的神经肽，FMRF-NH 2样肽的存在， 与四肽FMRF-NH 2不同，在哺乳动物CNS中， 众所周知。 为了进一步探讨内源性 FMRF-NH 2样免疫反应性在阿片类镇痛中的作用，我们已经确定 对哺乳动物FMRF-NH 2样肽进行化学表征。 两种新型 对FMRF-NH 2抗血清具有免疫反应性的肽， 从牛脑中纯化至均一，并测定其氨基酸序列 测定 此外，这两种肽（八肽和 十八肽）的合成和生物活性进行了测试， 大鼠 两种肽，当脑室内注射时，发现 减少大鼠甩尾次数。 其中一种肽，八肽， 能明显减弱吗啡的镇痛作用。 这种新的抗阿片作用的分子机制 哺乳动物FMRF-NH 2样肽是目前研究的对象。