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素 他们对包括艾滋病在内的机会性感染的脆弱性。至 到目前为止，对于免疫调节的机制还没有明确的解释 虽然纳洛酮，B-内啡肽的结合部位， 据报道，5-脑啡肽和布雷马佐辛存在于淋巴组织中。 细胞膜。这些结合位点在以下方面存在显著差异 中枢阿片受体的配基特异性和亲和力 神经系统(CNS)。探讨淋巴细胞/阿片类药物的作用机制 在互动方面，将采用三种一般方法。第一, 因为未激活的细胞缺乏这种免疫调节剂的结合部位 作为吗啡，人外周T淋巴细胞将被激活为细胞 用普通有丝分裂原或受体特异性药物进行分割，看看是否 激活刺激吗啡的结合位点的存在 纳洛酮。第二，高发的位置、性质和特殊性 淋巴细胞上亲和力、纳洛酮可逆结合部位的研究 通过离心法获得的亚细胞部分，其特征是 特异性酶和阿片结合试验，第三，T细胞的能力 将研究淋巴细胞对吗啡的摄取是否有一个途径 后跟绑定的内部化提供了对 未能检测到膜表面结合。这三种方法 将被用来定义吗啡的结合部位(受体) 与其可逆的纳洛酮免疫调节特性类似。一次 吗啡接触的证据是根据激活的有丝分裂原来定义的 与未激活的细胞、表面结合与摄取，以及 最大结合的亚细胞位置，然后特异性和 这种相互作用的亲和力可以通过药理学方法来评估。 在中枢神经系统中使用已知受体特异性的配体。这些 实验很重要，因为目前还没有数据来解释 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/阿片效应的最常用药物和 与街头鸦片成瘾最相关的鸦片类药物。最后，知识 配基的特异性在设计中将是重要的 没有免疫作用的麻醉药。

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.