OPIOID RECEPTORS ON LYMPHOCYTES

淋巴细胞上的阿片受体

• 批准号: 6137799
• 负责人: RONALD Y CHUANG
• 金额: $ 25.47万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6137799
• 关键词: G protein; Macaca mulatta; cyclic AMP; cytokine; dynorphins; enzyme activity; hybrid cells; immunopharmacology; lymphocyte; methadone; morphine; opioid receptor; phospholipase C; polymerase chain reaction; protein kinase C; receptor binding; receptor coupling; receptor expression; simian AIDSs; simian immunodeficiency virus; southern blotting; virus load

Drug abuse has been identified as a significant exacerbating factor in promoting the development of AIDS. The long-term goal of our research is to investigate the underlying mechanism of the effect of drugs such as opioids on attenuating host immune function. Preliminary studies on the molecular basis of the opioid effect on the progression of AIDS have led to our discovery of the expression of brain-like opioid receptors on lymphocytes, the cells of the immune system. The purpose of this proposal is to further characterize these receptors and study the factors involved in the regulation of lymphocyte opioid receptors. The specific aims of this research are (l) to determine the effect of chronic morphine and methadone administration on the expression of opioid receptors in monkey lymphocytes in vivo and in vitro, (2) to determine the effect of morphine, methadone and dynorphin treatment on the expression of opioid receptors using the CEM x174 cell line, a human T and B hybrid cell line susceptible to SIV infection, and (3) to determine the effect of opiate treatment on cytokine production and the G-protein-coupled signalling pathway of immune cells (monkey lymphocytes and CEM x174 cells). Methods to be used include the identification of receptor binding sites on immune cells in correlation with the presence of receptor mRNA, quantitative assays of cytokine release and protein kinase C/phospholipase C activity, and measurements of the up/down regulation of lymphocyte opioid receptors as influenced by SIV viremia after morphine, methadone or dynorphin treatment. Data obtained from this study will provide significant information toward our understanding of the relationship between opioid abuse and the complex brain immune axis, and this study may lead to the development of new therapeutic and prophylactic strategies in controlling AIDS and AIDS-related diseases.

药物滥用已被认为是 促进艾滋病的发展。我们研究的长期目标是 为了研究药物作用的潜在机制，如 阿片类药物对减弱宿主免疫功能的作用。关于黄曲霉毒素的初步研究 阿片类药物在艾滋病进展中作用的分子基础 我们发现脑内类阿片受体在脑内的表达 淋巴细胞，免疫系统的细胞。这项建议的目的是 是进一步确定这些受体的特征并研究涉及的因素 在调节淋巴细胞阿片受体方面。的具体目标 本研究旨在探讨(L)对慢性吗啡的影响。 美沙酮对猴阿片受体表达的影响 体内和体外淋巴细胞，(2)确定吗啡的作用。 美沙酮和强啡肽对阿片受体表达的影响 用CEM x174细胞株建立人T、B杂交瘤细胞系 (3)确定阿片类药物治疗对SIV感染的影响。 细胞因子产生与免疫G蛋白偶联信号通路 细胞(猴淋巴细胞和CEM x174细胞)。要使用的方法包括 人免疫细胞表面受体结合部位的鉴定 与受体mRNA存在的相关性，定量检测 细胞因子释放和蛋白激酶C/磷脂酶C活性，以及 淋巴细胞阿片受体上调/下调的检测方法 吗啡、美沙酮或强啡肽后SIV病毒血症的影响 治疗。从这项研究中获得的数据将提供重要的 对我们理解阿片类药物之间关系的信息 滥用和复杂的大脑免疫轴，这项研究可能导致 控制的新的治疗和预防策略的发展 艾滋病和艾滋病相关疾病。