COMPARISON OF OPIATE/OPIOID RECEPTORS IN THE ANS AND CNS

这是1R01 NS18017-01的重新提交，该文件已获得良好的批准 优先，但不提供资金。该提案已在 结合进一步的前期工作和研究部分的建议。最基本的 研究的目的是分离和表征，在 亚细胞来源的阿片和阿片受体的分子水平 CNS和ANS神经组织的部分。目前的证据表明 中枢神经系统和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。我们将首先集中讨论编程使用 确定总分子特征的辐射灭活技术 不同组织中的受体。超越这一步的将是 抗受体单抗的制备、纯化、分离及鉴定 抗体。这些将被用作研究受体的工具 组织中的异质性存在于受体的更详细的位置。他们还将 作为更详细的体内生理工作的起点 在此授权期之后执行。我们还将使用这些材料作为 亲和纯化试剂在受体分离中的应用 大分子。此外，我们将与至少一个其他公司合作 开发阿片/阿片受体新配体的实验室 这将有助于我们获得更完整和可靠的描述 他们的财产。特别是，我们考虑到可能的发展 对Mu、Delta或具有选择性相互作用轮廓的配体 Kappa受体。我们的长期目标是理解 阿片/阿片配基作用后神经膜中的分子事件 以及它们与中枢神经系统的整合(如脊髓-丘脑，以及 棘网状丘脑痛觉通路)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).