REGULATION OF KAPPA OPIOID RECEPTORS

描述：（申请人摘要） 阿片受体暴露于阿片肽或阿片生物碱 启动生物反应。 长期或反复接触 阿片类药物会导致对该药物的敏感性降低，从而导致 细胞反应；这种脱敏是由多种机制调节的 这与宽容和普遍发展有关 成瘾。 急性阿片类药物治疗可导致快速脱敏 受体与效应系统的功能性解偶联。 在 此外，这种治疗导致受体快速内化 进入细胞内区室。 慢性阿片类药物治疗会导致更长的时间 由于受体下调且结合净损失而导致脱敏 来自细胞的位点。 人们对分子的了解相对较少 这些事件背后的机制。 拟议研究的目标 这里是探索导致受体的激动剂介导的事件 内化和退化。 这些研究旨在探索 阿片受体内化和二聚化的分子机制 以便了解这些事件的功能意义。 的 具体目标是： (i) 描述 kappa 阿片受体贩运的特征 神经元细胞，以及 (ii) 探索二聚化在卡帕阿片类药物中的作用 受体功能。 这项工作将提供有关 调节阿片受体功能的早期激动剂介导的事件。 一个 彻底了解参与调节的细胞机制 受体脱敏对于治疗药物的开发至关重要 毒瘾的基础。

DESCRIPTION: (Applicant's Abstract) The exposure of an opioid receptor to opioid peptides or opiate alkaloids initiates a biological response. A long-term or repeated exposure to opioids causes a decreased sensitivity to the drug, leading to a reduced cellular response; this desensitization is regulated by multiple mechanisms which have been implicated in the generalized development of tolerance and addiction. Acute opioid treatments result in a rapid desensitization by functional uncoupling of the receptor from the effector system. In addition, this treatment results in a rapid internalization of the receptor into intracellular compartments. Chronic opioid treatment results in longer desensitization due to receptor down-regulation with a net loss of binding sites from the cell. Relatively little is known about the molecular mechanisms underlying these events. The objective of the studies proposed here is to explore the agonist-mediated events that lead to receptor internalization and degradation. These studies propose to explore the molecular mechanisms of opioid receptor internalization and dimerization in order to understand the functional significance of these events. The specific aims are: (i) to characterize kappa opioid receptor trafficking in neuronal cells, and (ii) to explore the role of dimerization in kappa opioid receptor function. This work will provide critical information about the early agonist-mediated events that modulate opioid receptor function. A thorough understanding of the cellular mechanisms involved in the modulation of receptor desensitization is crucial for the development of a therapeutic basis for drug addiction.