CELLULAR ASPECTS OF OPIATE BINDING TO HUMAN LEUKOCYTES

在近一个世纪的积累证据表明，吸毒使 人类容易发生机会性感染，目前尚不清楚 确切地说，哪些机制对这种易感性负责。这个 成瘾环境，包括营养不良和针头脏，两者都有 鸦片类药物对免疫系统的间接和直接影响一直是 作为这一现象的一部分，有积极的牵连。不管怎么说都很少 实际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行为的机制(S) 豁免权充其量只能说是模糊的。最近发现了一种诱导性的 丝裂原活化T淋巴细胞上的吗啡受体及其缺失 未激活的人类外周血淋巴细胞上的一种受体提供 研究直接阿片类药物作用的起点。三个目标 这样的研究将包括：L.定义特定细胞的研究 包含可诱导吗啡结合位点的种群(S)和TO 建立该部位的药理学特异性；2.尝试 通过比较激活的大鼠脑内的mRNA库克隆吗啡结合部位 和未激活的细胞使用减法技术，试图 确定该位点的信使核糖核酸；以及3.对过程的调查 缺乏吗啡结合部位的细胞对阿片类药物有反应。在这 在后一种情况下，已经发现吗啡可以被细胞摄取 在这一点上，吗啡可以与内部亚细胞结合 组分，例如，微生物体，并推测影响内部 细胞的代谢。随着机会性疾病的兴起，如 对艾滋病和抗生素耐药结核病，充分发挥作用变得重要 了解鸦片类药物和其他药物滥用的机制 (可卡因)损害免疫系统。明显不同的化学物质 需要对基于受体的机制和涉及 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.