On the evolution of opioid mechanisms and immune defenses.
On the evolution of opioid mechanisms and immune defenses.
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关于阿片类药物机制和免疫防御的演变。
DOI：
10.1007/978-1-4613-0407-4_10
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发表时间：
1996
影响因子：
--
通讯作者：
Tomei,EZ
中科院分区：
文献类型：
--
作者：
Renaud,FL;Tomei,EZ
我们实验室的结果表明，阿片调节的吞噬作用起源于进化的早期，这一机制的基本方面一直是保守的。在纤毛虫四膜虫中检测到的β-内啡肽样免疫反应似乎调节吞噬作用。我们比较了阿片类药物对四膜虫吞噬功能和Fc介导的小鼠巨噬细胞吞噬功能的影响。这些效应非常相似：a)阿片激动剂通过纳洛酮可逆机制抑制吞噬作用，有效浓度在纳摩尔范围内；b)急性暴露的作用是剂量依赖性和双相性的；c)长期接触吗啡会导致类似脱敏和耐受的状态；d)在某些情况下，吗啡对耐受细胞的作用可能是刺激的；e)从耐受细胞中撤除吗啡可能会抑制吞噬作用，这表明耐受细胞可能需要吗啡在基础水平上执行这一功能。药理学数据表明，四膜虫中的阿片受体类似于Mu，可能与Gi样蛋白有关，因为百日咳毒素预处理将抵消阿片类物质的抑制作用。我们的工作表明，阿片类药物对免疫系统的影响起源于进化的早期，因为吞噬作用可能被认为是原始细胞防御机制。
Results from our laboratory suggest that opioid-modulated phagocytosis originated early in evolution and fundamental aspects of this mechanism have been conserved. β-endorphin-like immunoreactivity detected in the ciliateTetrahymenaappears to modulate phagocytosis. We have compared the effects of opioids on phagocytosis inTetrahymenaand in Fc-mediated phagocytosis by peritoneal murine macrophages. These effects are remarkably similar: a) opioid agonists inhibit phagocytosis by a naloxone-reversible mechanism with effective concentrations in the nanomolar range, b) the effect of acute exposure is dose-dependent and biphasic, c) chronic exposure to morphine results in a state akin to desensitization and tolerance, d) the effect of morphine on tolerant cells may be stimulatory under certain circumstances, e) withdrawal of morphine from tolerant cells may inhibit phagocytosis suggesting that tolerant cells may require morphine to perform this function at a basal level. Pharmacological data suggest that the opioid receptor inTetrahymenais mu-like and may be associated with a Gi-like protein since pertussis toxin pre-treatment will counteract the inhibitory effect of opioids. Our work suggests that the influence of opioids on the immune system originated early in evolution since phagocytosis may be considered the primeval cell defense mechanism.