PHE-MET-ARG-PHE-NH2 LIKE PEPTIDES IN CNS--FUNCTION AND DISTRIBUTION

中枢神经系统中的 PHE-MET-ARG-PHE-NH2 样肽--功能和分布

• 批准号: 3859866
• 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/3859866
• 关键词: analgesia; antiserum; arginine vasopressin; brain mapping; developmental neurobiology; drug tolerance; endorphins; inhibitor /antagonist; laboratory mouse; laboratory rat; molecular genetics; morphine; neural transmission; neuropeptides; neuropharmacology; pituitary gland; supraoptic nucleus

The neuropeptide FLFQPQRF-NH(F-8-F-NH2) was originally isolated from the bovine brain and found to have morphine modulating activity. F-8-F-NH2 is highly localized in nerve terminals in posterior pituitary. The source of this pituitary F-8-F-NH2 was studied by various lesions. Our results suggest that at least part of the pituitary F-8-F-NH2 originates from supraoptic nuclei where it may be co-localized with Arg8-vasopressin. The role of F-8-F-NH2 in morphine tolerance and defeat-induced analgesia was studied using IgG from F-8-F-NH2 antiserum as antagonist. Injection (ICV) of IgG from F-8-F-NH2 antiserum restored the analgesic response to morphine in morphine-tolerant rats suggesting that endogenous F-8-F-NH2 contributes to morphine tolerance. Injection (ICV) of F-8-F-NH2 attenuated the defeat induced analgesia in the subordinate mice during the agonistic encounter. In contrast, ICV administration of IgG from F-8-F-NH2 antiserum augmented the levels of defeat induced analgesia. These results provide further evidence that F-8-F-NH2 may have a modulatory role in endogenous opioid mediated analgesia. Development of F-8-F-NH2 was studied in the rat CNS. F-8-F-NH2 was not detected in the brain or the spinal cord before the 18th embryonic day. The first F-8-F-NH2 positive fibers and terminals were detected in the median eminence on the 20th embryonic day. Postnatally, F- 8-F-NH2 system developed rapidly both in the brain and spinal cord, and was adult like by the age of 4 weeks. The late appearance of F-8-F-NH2 system during the ontogeny suggests that these peptides are expressed in relatively mature neurons. These results further imply that F-8-F-NH2 may not have a general function in the development of the nervous system, but rather may act as a neuromodulator or neurotransmitter since its production starts in neurons.

神经肽FlFQPQRF-NH(F-8-F-NH2)最初是从 牛脑，并发现具有吗啡调节活性。F-8-F-NH2是 高度定位于垂体后叶的神经末梢。的来源 对这种垂体F-8-F-NH2进行了各种病变的研究。我们的结果 提示至少部分脑垂体F-8-F-NH2起源于 视上核，可能与Arg8-加压素共同定位。这个 F-8-F-NH2在吗啡耐受和失败性镇痛中的作用 以F-8-F-NH_2抗血清中的免疫球蛋白作为拮抗剂进行研究。注射(Icv) 应用F-8-F-NH2抗血清中的免疫球蛋白恢复吗啡的镇痛效应 在吗啡耐受大鼠中，提示内源性F-8-F-NH2参与 对吗啡的耐受性。侧脑室注射F-8-F-NH2可减轻这种失败 在激动性相遇中诱导从属小鼠的镇痛。 相反，侧脑室注射来自F-8-F-NH2抗血清的免疫球蛋白增加 失利的程度导致了镇痛。这些结果进一步提供了 F-8-F-NH2可能对内源性阿片类药物具有调节作用的证据 中介止痛。本文研究了F-8-F-NH_2在大鼠中枢神经系统的发育。 在18日之前，大脑和脊髓中都没有检测到F-8-F-NH2 胚胎日。第一批F-8-F-NH2阳性纤维和终末为 在胚胎第20天在正中隆起中检测到。出生后，F- 8-F-NH2系统在脑和脊髓中迅速发展，并在 4周大的时候就成年了。F-8-F-NH_2体系出现较晚 在个体发育过程中表明这些多肽在 相对成熟的神经元。这些结果进一步表明，F-8-F-NH2可能 在神经系统的发育过程中没有普遍的作用，但 而是可以作为神经调节剂或神经递质，因为它产生 开始于神经元。