PHE-MET-ARE-PHE-NH2 LIKE PEPTIDES IN THE BRAIN AND SPINAL CORD

大脑和脊髓中的 PHE-MET-ARE-PHE-NH2 样肽

• 批准号: 3944684
• 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/3944684
• 关键词: analgesia; brain; catecholamines; immunochemistry; neural transmission; neuropharmacology; neurotransmitter biosynthesis; oligopeptides; pain threshold; prazosin; radioimmunoassay; spinal cord; vasoconstrictors; vasodilators

We have previously isolated from bovine brain and chemically characterized two putative endogenous opiate antagonist peptides. These peptides, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe- NH2 and Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala- Ala-Pro-Gln-Arg-Phe-NH2, were found to be highly localized in periaqueductal gray and dorsal spinal cord, areas important for opiate antinociception. In this study, distribution and pathways of these two peptides in rat spinal cord were studied in detail by radioimmunoassay and immunohistochemistry. Levels of these two peptides are highest in dorsal gray and lowest in ventral white. After spinal cord transection, levels of these two peptides decreased significantly caudal to the transected region indicating the presence of descending pathways of these two peptides. Immunohistochemically, intense immunoreactivity was observed in substantia gelatinosa of posterior horn, scattered fibers were found in deeper laminae of posterior horn. The morphological study further suggests the possible role of these two peptides in opiate mediated analgesia. In further studying the biological property of these two peptides, they were found to elevate mean arterial blood pressure. This pressor activity was attenuated by prior treatment with guanethidine or prazocin. The results suggest that these two peptides increase mean arterial pressure by potentiating the release of catecholamines. The proposed course of this study is to investigate the mechanism by which these two peptides act to modulate opiate analgesia including release of these two peptides from spinal cord and receptors for these two peptides.

我们之前已经从牛脑中分离出来并用化学方法 表征了两种假定的内源性阿片拮抗剂 肽。 这些肽，Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe- NH2 和 Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala- Ala-Pro-Gln-Arg-Phe-NH2，被发现高度定位于 导水管周围灰质和背侧脊髓，重要区域 阿片类镇痛药。 在这项研究中，分布和途径 大鼠脊髓中的这两种肽经过详细研究 放射免疫分析和免疫组织化学。 这些的水平 两种肽在背侧灰色最高，在腹侧最低 白色的。 脊髓横断后，这两种肽的水平 尾部显着减少到横切区域表明 这两种肽的下行通路的存在。 免疫组织化学观察到强烈的免疫反应性 后角胶质质内有散在的纤维 发现于后角较深的椎板。 形态学 研究进一步表明这两种肽在 阿片介导的镇痛。 在进一步研究这两种肽的生物学特性时， 研究发现它们会升高平均动脉血压。 这 升压活性因先前的治疗而减弱 胍乙啶或哌佐星。 结果表明，这两个 肽通过增强平均动脉压 儿茶酚胺的释放。 本研究的拟议课程是研究其机制 这两种肽通过这两种肽来调节阿片镇痛 包括从脊髓释放这两种肽 这两种肽的受体。