TYR-W-MIF-1 AND OPIATE TOLERANCE

TYR-W-MIF-1 和阿片类药物耐受性

• 批准号: 2713071
• 负责人: SHERYL B MARTIN-SCHILD
• 金额: $ 1.84万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2713071
• 关键词: autoradiography; cerebrospinal fluid; drug tolerance; gene induction /repression; laboratory rat; morphine; naloxone; neuropeptide receptor; neuropeptides; neuropharmacology; opioid receptor; protooncogene; radioimmunoassay; receptor binding; receptor expression

Tyr-W-MIF-1, (Tyr-Pro-Trp-Gly-NH2), is a unique brain peptide in that it acts as an opiate agonist in the opiate-naive animal, but can antagonize morphine and other opiates in the opiate-tolerant animal. Tyr-W-MIF-1 binds to the mu opiate receptor as well as its own "anti-opiate" receptor. The anatomical sites of action of the peptide will be elucidated by three approaches. Brain regions containing a relative abundance of Tyr-W-MIF-1 will be identified by radioimmunoassay and immunocytochemistry, using an antibody generated and characterized in this lab. Tyr-W-MIF-1 anti-opiate receptor sites will also be localized by quantitative receptor autoradiography. Neuronal activation by Tyr-W-MIF-1 will be determined by FOS immunocytochemistry, and will be separated into opiate and non-opiate components by injection with or without naloxone. Because the role of the peptide changes from opiate agonist to opiate antagonist after tolerance to morphine develops, we propose that Tyr-W-MIF-1 concentrations, anti- opiate receptors, and neuronal activation are altered by the development of morphine tolerance. Demonstration that Tyr-W-MIF-1 is a crucial element in the development of morphine tolerance will aid our understanding of the basic mechanisms of the phenomenon, with implications for new therapies for pain and addiction.

Tyr-W-MIF-1（Tyr-Pro-Trp-Gly-NH2）是一种独特的脑肽 在非鸦片动物中充当鸦片激动剂，但可以拮 吗啡和其他阿片类动物中的其他阿片类动物。 Tyr-W-Mif-1 与MU鸦片受体及其自身的“抗焦型”受体结合。 肽的解剖作用部位将由三个 方法。大脑区域含有相对丰度Tyr-W-Mif-1 将使用放射免疫测定和免疫细胞化学来识别 在本实验室中生成和表征的抗体。 Tyr-W-MIF-1抗居民 受体位点也将通过定量受体定位 放射自显影。 Tyr-W-MIF-1的神经元激活将由 FOS免疫细胞化学，并将分为阿片类药物 通过或不带有纳洛酮的注射组件。因为 肽从阿片激动剂变为鸦片拮抗剂后的肽变化 对于吗啡的发展，我们建议Tyr-W-MIF-1浓度，抗 鸦片受体和神经元激活因发育而改变 吗啡耐受性。演示Tyr-W-Mif-1是关键元素 在发展吗啡的发展中，将有助于我们理解 现象的基本机制，对新疗法有影响 疼痛和成瘾。