COMPARISON OF OPIATE/OPIOID RECEPTORS IN THE ANS AND CNS

这是1 R 01 NS 18017 -01的重新提交，已获得良好批准 优先，但没有资金。 该提案已在 根据进一步的初步工作和研究部分的建议。 基本 研究的目的是分离和表征，在 分子水平，阿片和阿片受体的亚细胞来源 CNS和ANS神经组织的部分。 目前的证据表明， CNS和ANS组织中存在多种阿片/阿片样物质受体需要 澄清，并密切结盟的综合现象，在两个 神经系统 我们将首先集中在编程使用 辐射灭活技术，以确定总体分子特征 不同组织中的受体。 除此之外， 抗受体单克隆抗体的制备、纯化、分离和鉴定 抗体的 这些将被用作研究受体的工具 组织中的异质性更详细地定位受体。他们还将 作为更详细的体内生理学工作的起点， 在此期间，在此期间， 我们还将使用这些材料作为 受体分离中的亲和纯化试剂 大分子 此外，我们还将与至少一个 阿片类药物/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。 特别是，我们考虑到可能发展 配体，其可以具有针对Mu、Delta或 κ受体。 我们的长期目标是了解 阿片/阿片配体受体介导的神经膜分子事件 以及它们整合到CNS中（如脊髓-丘脑，和 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）。

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).