CELLULAR ASPECTS OF OPIATE BINDING TO HUMAN LEUKOCYTES

经过近世纪的积累， 人类容易受到机会性感染，目前尚不清楚 确切地说，是什么机制导致了这种易感性。的 成瘾环境，包括营养不良和肮脏的针头，以及两者兼而有之 阿片类药物对免疫系统的间接和直接影响， 积极地参与了这一现象。然而， 实际上证明了这些因素中每一个的相对贡献。 特别是，阿片类药物直接调节人类免疫功能的机制， 免疫充其量是模糊。最近发现的一种可诱导的 有丝分裂原激活的T淋巴细胞上的吗啡受体和缺乏这种受体 非活化的人外周淋巴细胞上的受体提供了 研究阿片类药物直接作用的起点。三个目标 这样的研究将包括：l。定义特定细胞的研究 含有诱导型吗啡结合位点的群体， 建立该部位的药理学特异性; 2.试图 通过比较激活的细胞中的mRNA库克隆吗啡结合位点， 和未活化的细胞，试图 鉴定该位点的mRNA;以及3.调查的过程中， 缺乏吗啡结合位点的细胞对鸦片有反应。在这 在后一种情况下，已经发现吗啡可以被细胞吸收， 此时吗啡可以与内部亚细胞结合 馏分，例如，微粒体，并推测影响内部 细胞的新陈代谢。随着机会性疾病的增加， 艾滋病和耐抗生素结核病，充分利用 了解鸦片和其他药物滥用的机制 （可卡因）危害免疫系统。明显不同的化学物质 需要对基于受体的机制进行干预， 吸收和内化。

After almost a century of accumulating evidence that drug addiction makes humans prone to opportunistic infections, it is still not known definitively which mechanisms are responsible for this susceptibility. The addiction milieu, including poor nutrition and dirty needles, and both indirect and direct effects of the opiates on the immune system have been positively implicated as part of this phenomenon. However little is actually proven as to the relative contributions of each of these factors. In particular, the mechanism(s) by which opiates directly modulate human immunity are at best obscure. The recent discovery of an inducible morphine receptor on mitogen activated T lymphocytes and the lack of such a receptor on nonactivated human peripheral lymphocytes provides a starting point for investigating the direct opiate effects. Three goals for such research would include: l. studies to define the specific cell population(s) containing the inducible morphine binding site and to establish the pharmacological specificity of the site; 2. an attempt to clone the morphine binding site by comparing mRNA pools in the activated and nonactivated cells using subtractive techniques in an attempt to identify the mRNA for this site; and 3. investigations of the processes by which the cells lacking morphine binding sites respond to opiates. In this latter case, it has been found that morphine can be taken up by the cells at which point the morphine can then bind to internal subcellular fractions, e.g., the microsomes, and presumptively affect the internal metabolism of the cell. With the rise of such opportunistic diseases as AIDS and antibiotic resistent tuberculosis, it becomes important to fully understand the mechanisms by which opiates and other drugs of abuse (cocaine) compromise the immune system. Clearly different chemical interventions are needed for receptor based mechanisms and those involving uptake and internalization.