OPIOID RECEPTORS ON LYMPHOCYTES

药物滥用已被确定为一个重要的加剧因素， 促进艾滋病的发展。 我们研究的长期目标是 研究药物作用的潜在机制， 阿片类药物减弱宿主免疫功能。 的初步研究 阿片类药物对艾滋病进展的作用的分子基础已经导致 我们发现大脑中类阿片受体的表达 淋巴细胞，免疫系统的细胞。 这项建议的目的 是进一步研究这些受体的特性， 在调节淋巴细胞阿片受体中的作用 的具体目标 本研究的目的是（1）确定慢性吗啡的作用， 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， 美沙酮和强啡肽治疗对阿片受体表达的影响 使用CEM x174细胞系，人T和B杂交细胞系易感 （3）确定阿片类药物治疗对SIV感染的影响， 细胞因子的产生和G蛋白偶联的免疫信号通路 细胞（猴淋巴细胞和CEM x174细胞）。 使用的方法包括 免疫细胞上受体结合位点的鉴定 与受体mRNA存在的相关性， 细胞因子释放和蛋白激酶C/磷脂酶C活性，以及 测量淋巴细胞阿片受体的上调/下调， 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 这些信息有助于我们理解阿片类药物 滥用和复杂的大脑免疫轴，这项研究可能会导致 开发新的治疗和预防策略， 艾滋病和与艾滋病有关的疾病。

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.