BRAIN OPIATE RECEPTOR PROPERTIES AND FUNCTION

脑阿片受体的特性和功能

• 批准号: 3069548
• 负责人: Bruce Lane Nock
• 金额: $ 5.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-04 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3069548
• 关键词: adrenocorticotropic hormone; autoradiography; brain mapping; brain metabolism; calcium channel; dynorphins; endorphins; guanine nucleotide binding protein; guinea pigs; high performance liquid chromatography; hormone regulation /control mechanism; laboratory rat; naltrexone; neurochemistry; neuropeptide receptor; neuropharmacology; protein structure function; radioimmunoassay; radiotracer; receptor binding

The research described focuses on two types of binding sites with high affinities for "kappa"-type opiate drugs. These sites appear to be separate entities since they differ in terms of biochemical and pharmacological characteristics and are differentially distributed in brain. One site has a high affinity for dynorphin and, therefore, corresponds to what has traditionally been termed the kappa receptor. The second site, which we refer to as T2 in this proposal, has opiate receptor characteristics but does not appear to be a kappa receptor since dynorphin and prodynorphin-related peptides have a low affinity for the site. The T2 site also has characteristics that clearly distinguish it from mu and delta opiate receptors. Thus, it is plausible that the T2 site is a major type of receptor for opiates which, heretofore, has been studied to only a limited extent. The endogenous ligand for T2 might be beta-endorphin since it has a much higher affinity for the site than other endogenous opioids. The studies in this proposal utilize recently developed drugs and procedures that distinguish between the K and T2 receptor and should contribute important information toward establishing the nature and characteristics of the sites and their biochemical and physiological functions. In addition, the latest tools of computational chemistry and molecular design be employed in the development of a truly-selective, high-affinity ligand for the T2 site. The availability of such a ligand will greatly facilitate studies of the site. We believe our extensive preliminary studies of the T2 and kappa binding sites give us a unique foundation for successfully carrying out the proposed project.

所描述的研究重点关注两种类型的高结合位点 对“kappa”型阿片类药物的亲和力。 这些网站似乎是 不同的实体，因为它们在生化和化学方面不同 药理特性和差异分布 脑。 一个位点对强啡肽具有高亲和力，因此， 对应于传统上称为 kappa 受体的东西。 这 第二个位点，我们在本提案中称为 T2，具有阿片受体 特征但似乎不是 kappa 受体，因为强啡肽 强啡肽原相关肽对该位点的亲和力较低。 T2 站点还具有明显区别于 mu 和 delta 的特征 阿片受体。 因此，T2位点是主要类型是合理的。 迄今为止，仅研究了阿片受体的 程度有限。 T2 的内源性配体可能是 β-内啡肽，因为 它对该位点的亲和力比其他内源性阿片类药物高得多。 本提案中的研究利用了最近开发的药物和 区分 K 和 T2 受体的程序，应 为建立自然和 部位特征及其生化和生理学 功能。 此外，计算化学的最新工具和 分子设计可用于开发真正选择性的、 T2 位点的高亲和力配体。 这种配体的可用性 将极大地方便该网站的研究。 我们相信我们广泛的 T2 和 kappa 结合位点的初步研究为我们提供了独特的 为成功实施拟议项目奠定了基础。