REGULATION OF KAPPA OPIOID RECEPTORS

KAPPA 阿片受体的调节

• 批准号: 2707525
• 负责人: BRYEN A JORDAN
• 金额: $ 2.53万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-05 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2707525
• 关键词: immunocytochemistry; intracellular transport; molecular cloning; neurons; opioid receptor; protein biosynthesis; protein structure function; protein transport; receptor expression; recombinant proteins; tissue /cell culture

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.

描述：（申请人摘要）