CELLULAR ASPECTS OF OPIATE BINDING TO HUMAN LEUKOCYTES

阿片类药物的免疫调节作用被认为是 阿片类药物成瘾者免疫缺陷的重要辅助因子， 他们容易受到机会性感染，包括艾滋病。 到 迄今为止，对免疫调节的机制还没有明确的解释， 尽管纳洛酮，B-内啡肽， 据报道，met 5-脑啡肽和布马佐辛存在于淋巴细胞上， 细胞膜 这些结合位点在以下方面显著不同： 配体特异性和亲合力从阿片受体的中央 神经系统（CNS）。 探讨淋巴细胞/阿片类药物的作用机制 互动，将采用三种一般方法。 第一、 因为未活化的细胞缺乏这种免疫调节剂的结合位点 与吗啡一样，人外周血T淋巴细胞会被激活， 与一般的有丝分裂原或受体特异性试剂分开， 激活刺激吗啡结合位点的存在， 纳洛酮 第二，位置，性质和特殊性高 亲和力，将研究纳洛酮在淋巴细胞上的可逆结合位点 通过离心获得的亚细胞级分，其特征在于 特异性酶和阿片结合试验，第三，T 将研究淋巴细胞摄取吗啡的途径， 内在化之后是结合的解释了 未能检测到膜表面结合。 这三种方法 将用于定义吗啡的结合位点（受体）， 平行纳洛酮可逆免疫调节特性。 一旦 吗啡接触的证据是根据有丝分裂原激活 与非活化细胞，表面结合与摄取，以及 最大结合的亚细胞位置，则特异性和 这种相互作用的亲合力可以通过药理学方法来评估 使用CNS中已知受体特异性的配体。 这些 实验很重要，因为目前没有数据可以解释 吗啡与淋巴细胞相互作用的机制，但吗啡是 用于证明体外免疫/阿片作用的最常用药物， 与街头鸦片成瘾最相关的鸦片 最后，知识 配体特异性的研究在设计 无免疫作用的麻醉剂。

The immunomodulatory actions of opiates have been implicated as significant cofactors in the immune deficiencies of opiate addicts and their vulnerability to opportunistic infections, including AIDS. To date, no clear explanation of the mechanism for the immunomodulation has emerged although binding sites for naloxone, B-endorphin, met5-enkephalin and bremazocine have been reported to exist on lymphoid cell membranes. These binding sites are significantly different in ligand specificity and avidity from the opiate receptors of the central nervous system (CNS). To investigate the mechanism of lymphocyte/opiate interactions, three general methodologies will be employed. First, because nonactivated cells lack binding sites for such immunomodulators as morphine, human peripheral T lymphocytes will be activated to cell division with general mitogens or receptor specific agents to see if activation stimulates the presence of binding sites for morphine and naloxone. Second, the location, nature and specificity of a high affinity, naloxone reversible binding site will be studied on lymphocyte subcellular fractions obtained by centrifugation and characterized by specific enzyme and opiate binding assays, Third, the ability of T lymphocytes to take up morphine will be studied to see whether a pathway of internalization followed by binding provides the explanation for the failure to detect membrane surface binding. These three methodologies will be used to define a binding site (receptor) for morphine to parallel its naloxone reversible immunomodulatory properties. Once evidence of morphine contact is defined in terms of mitogen activated versus nonactivated cells, surface binding versus uptake, and the subcellular location of maximal binding, then the specificity and avidity of this interaction can be assessed by pharmacologic methods using ligands of known receptor specificity in the CNS. These experiments are important because no data currently exist to explain the mechanism of morphine's interaction with lymphocytes, yet morphine is the most used drug for demonstrating in vitro immune/opiate effects and the opiate most relevant to street opiate addiction. Finally, knowledge of the ligand specificity would be important in the design of anesthetics without immune effects.