Sharp B M, Roy S, Bidlack J M
Endocrine-Neuroscience and Neuroimmunomodulation Research Labs., Minneapolis Medical Research Foundation, MN 55404, USA.
J Neuroimmunol. 1998 Mar 15;83(1-2):45-56.
Although the role of opiates and opioids in the physiological and pathological function of the immune system is only beginning to be unraveled, converging lines of evidence indicate that the opioid receptors expressed by immune cells are often the same or similar to the neuronal subtypes, particularly delta and kappa. Recent studies also point to the existence of novel opioid receptors and/or binding sites on immune cells that are selective for morphine. Opioids and their receptors, particularly those with high affinity for delta agonists, appear to function in an autocrine/paracrine manner. Thus, opioid peptides generated from immune-derived proenkephalin A act as cytokines, capable of regulating myriad functions of both granulocytes and mononuclear cells. Further identification and characterization of receptors and signal transduction pathways that account for some of the unique properties of opiate binding and immunomodulation (e.g., dose-dependent effects of morphine that occur at exceptionally low concentrations relative to the Kd's of the neuronal mu receptor or the morphine binding site reported on activated human T-cells) represents one of the major research challenges ahead. Elucidating mechanisms, such as these, may provide unique therapeutic opportunities through the application of opioid immunopharmacology to disorders involving immune responses in peripheral organs and the central nervous system.
尽管阿片类药物在免疫系统的生理和病理功能中的作用才刚刚开始被揭示，但越来越多的证据表明，免疫细胞表达的阿片受体通常与神经元亚型相同或相似，尤其是δ和κ亚型。最近的研究还指出，免疫细胞上存在对吗啡具有选择性的新型阿片受体和/或结合位点。阿片类药物及其受体，特别是那些对δ激动剂具有高亲和力的受体，似乎以自分泌/旁分泌方式发挥作用。因此，从免疫来源的前脑啡肽A产生的阿片肽作为细胞因子，能够调节粒细胞和单核细胞的多种功能。进一步鉴定和表征那些解释阿片结合和免疫调节某些独特特性的受体和信号转导途径（例如，相对于神经元μ受体的Kd值或活化的人T细胞上报道的吗啡结合位点，吗啡在极低浓度下产生的剂量依赖性效应）是未来的主要研究挑战之一。阐明诸如此类的机制，可能通过将阿片免疫药理学应用于涉及外周器官和中枢神经系统免疫反应的疾病，提供独特的治疗机会。
