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首页> 外文期刊>Life sciences >Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions
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Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions

机译：新型非肽类阿片样物质4-酪氨酰氨基-6-苄基-1,2,3,4四氢喹啉（CGPM-9）对体外大鼠t淋巴细胞和巨噬细胞功能的差异作用

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Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opioid agonists such as morphine are immunosuppressive, whereas certain 6-opioid receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the non-peptidic 6-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahy-droquinoline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanavalin A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reduction) by peritoneal macrophages, compared with untreated control. The mu -opioid receptor selective antagonist CTOP used at equimolar doses, significantly suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (CTOP alone did not show any effect on lymphocyte or macrophage functions). In summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu -opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathways depending on the cell type and effector function being analyzed. The mechanism(s) associated with the differential effect of CGPM-9 on these immune cells remains to be elucidated. The pharmacotherapeutic potential for compounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppress production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine. (C) 2001 Elsevier Science Inc. All rights reserved. [References: 40]
机译：阿片样物质受体已经在几种物种的免疫细胞上被报道，并显示出可以辅助这些细胞类型的效应子功能。 Mu选择性阿片类激动剂（例如吗啡）具有免疫抑制作用，而某些6类阿片类受体选择性激动剂则具有免疫增强作用。先前我们已经证明，非肽6阿片类受体激动剂的脑室内给药不会改变免疫能力的某些参数。在这项研究中，我们评估了新型非肽类阿片样物质4-酪氨酰氨基-6-苄基-1,2,3,4四氢喹啉（CGPM-9）对淋巴细胞和巨噬细胞功能的体外作用。我们证明CGPM-9可增强大鼠对刀豆球蛋白A的胸腺淋巴细胞增殖反应（增加2.85至5.5倍），并抑制LPS诱导的一氧化氮（减少67％至72％）和TNF-α产生（减少46％）。腹膜巨噬细胞，与未经处理的对照相比。以等摩尔剂量使用的μ阿片类受体选择性拮抗剂CTOP显着抑制了CGPM-9对淋巴细胞和巨噬细胞功能的影响（仅CTOP并未显示对淋巴细胞或巨噬细胞功能的任何影响）。总之，CGPM-9通过作用于μ阿片样物质受体而激活胸腺淋巴细胞增殖并抑制巨噬细胞功能。这表明免疫细胞上的阿片样物质受体可能取决于所分析的细胞类型和效应子功能而与不同的信号通路偶联。与CGPM-9对这些免疫细胞的差异作用有关的机制还有待阐明。在研究和临床医学中，对于能够增强T淋巴细胞增殖并抑制巨噬细胞源性炎性细胞因子产生的CGPM-9等化合物而言，其药物治疗潜力很大。 （C）2001 Elsevier Science Inc.保留所有权利。 [参考：40]

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