Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells.
Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells.
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DOI：
10.1006/excr.2002.5638
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发表时间：
2002-11
影响因子：
3.7
通讯作者：
Shunji Suzuki;L. Chuang;P. Yau;R. Doi;R. Chuang
中科院分区：
文献类型：
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作者：
Shunji Suzuki;L. Chuang;P. Yau;R. Doi;R. Chuang
吗啡对阿片受体的激活以前被证明可以特异性地诱导趋化因子受体CCR 5的表达，促进猿艾滋病病毒进入免疫细胞并在免疫细胞中复制。本研究的目的是确定这两种结构和功能不同的G蛋白偶联受体是否非常接近，并在细胞膜上形成寡聚复合物，以便一种受体的激活触发另一种受体的活性。在本研究中使用了人CEM x174和猴淋巴细胞，结果相似。免疫沉淀实验表明，CCR 5，而不是CD 4或Na（+）/H（+）交换剂，与阿片受体的所有三种亚型（μ，δ和κ）共沉淀。在非变性聚丙烯酰胺凝胶上电泳后，确定了一个单一的蛋白带免疫反应性抗体对CCR 5和阿片受体。用戊二醛或BS（3）进行的化学交联实验表明，这些受体紧密地位于细胞膜上，分子间距离小于11.4A。功能研究表明，联合治疗的细胞与吗啡，激动剂μ，MIP-1 β，CCR 5的配体，抑制MIP-1 β的抑制作用，并增加吗啡对CCR 5表达的刺激作用。这些结果表明，趋化因子受体CCR 5和阿片受体在人或猴淋巴细胞的细胞膜上的寡聚化可以调节受体功能。
Activation of opioid receptors by morphine was previously shown to specifically induce the expression of chemokine receptor CCR5, promoting simian AIDS virus entry and replication in immune cells. The present study was undertaken to determine whether these two structurally and functionally distinct G-protein-coupled receptors are in close proximity and form an oligomeric complex in the cell membrane so that the activation of one triggers the activity of the other. Both human CEM x174 and monkey lymphocytes were used in this study and gave similar results. Immunoprecipitation experiments showed that CCR5, but not CD4 nor Na(+)/H(+) exchanger, coprecipitates with all three subtypes (mu, delta, and kappa) of opioid receptors. A single protein band immunoreactive with antibodies against both the CCR5 and the opioid receptors was identified after electrophoresis on nondenaturing polyacrylamide gels. Chemical crosslinking experiments using glutaraldehyde or BS(3) indicate that these receptors are closely situated on the cell membrane with an intermolecular distance less than 11.4A. Functional studies revealed that a combination treatment of cells with morphine, an agonist for mu, and MIP-1beta, a ligand for CCR5, suppresses the inhibitory effect of MIP-1beta and increases the stimulatory effect of morphine on CCR5 expression. These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors on the cell membrane of human or monkey lymphocytes may modulate receptor functions.