COMPARISON OF OPIATE/OPIOID RECEPTORS IN THE ANS AND CNS

ANS 和 CNS 中阿片/阿片类药物受体的比较

• 批准号: 3398046
• 负责人: JAY A GLASEL
• 金额: $ 7.41万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3398046
• 关键词: affinity chromatography; autonomic nervous system; central nervous system; fluorescence; hybridomas; ligands; monoclonal antibody; neuroanatomy; radioimmunoassay; scintillation counter; spectrometry

This is a resubmission of 1R01 NS18017-01 which was approved with good priority but not funded. The proposal has been revised and updated in the light of further preliminary work and study section suggestions. The basic objective of the research is the isolation and characterization, at the molecular level, of opiate and opioid receptors derived from subcellular fractions of CNS and ANS neural tissue. The current evidence for the existence of multiple opiate/opioid receptors in CNS and ANS tissue demands clarification and is closely allied with integrative phenomena in both nervous systems. We will first concentrate on a programmed use of radiation inactivation techniques to determine the gross molecular features of receptors in the different tissues. The step beyond this will be to raise, purify, isolate and characterize monoclonal anti-receptor antibodies. These will be used as tools for investigating receptor heterogeneity in tissue situated receptors in more detail. They will also serve as starting points for more detailed in vivo physiological work to be carried out beyond this grant period. We will also use these materials as affinity purification reagents in the isolation of receptor macromolecules. In addition, we will collaborate with at least one other laboratory on the development of new ligands for opiate/opioid receptors which would aid us in obtaining more complete and reliable characterization of their properties. In particular we have in mind possible development of ligands which may have selective interaction profiles towards Mu, Delta or Kappa receptors. Our long range goal is understanding the sequence of molecular events in neuromembranes following opiate/opioid ligand reception and their integration into the CNS (as exemplified by spino-thalamic, and spino-reticulo thalamic pain pathways) and ANS (as exemplified by the relationships between visceral-sensory and visceral-motor pathways).

这是 1R01 NS18017-01 的重新提交，已获得良好批准 优先但没有资助。 该提案已在《建议》中进行了修改和更新 根据进一步的前期工作和研究部分的建议。 基本的 研究的目的是分离和表征 分子水平，源自亚细胞的阿片和阿片受体 CNS 和 ANS 神经组织的部分。 目前的证据表明 CNS 和 ANS 组织需求中存在多种阿片/阿片受体 澄清并与两者的综合现象密切相关 神经系统。 我们首先将集中精力于程序化的使用 辐射灭活技术以确定总体分子特征 不同组织中的受体。 超越此的步骤将是 培养、纯化、分离和表征单克隆抗受体 抗体。 这些将用作研究受体的工具 更详细地了解组织中受体的异质性。他们还将 作为更详细的体内生理工作的起点 在此资助期限之后进行。 我们还将使用这些材料 亲和纯化试剂在受体分离中的应用 大分子。 此外，我们将与至少另一家合作 阿片/阿片受体新配体开发实验室 这将有助于我们获得更完整和可靠的表征 他们的财产。 我们特别考虑到可能的发展 可能对 Mu、Delta 或具有选择性相互作用特征的配体 Kappa 受体。 我们的长期目标是了解 阿片/阿片配体接受后神经膜的分子事件 以及它们与中枢神经系统的整合（以脊髓丘脑为例， 脊髓网状丘脑疼痛通路）和 ANS（如 内脏感觉和内脏运动通路之间的关系）。