Makman M H
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
Adv Neuroimmunol. 1994;4(2):69-82. doi: 10.1016/s0960-5428(05)80002-6.
Receptor interactions of morphine are reviewed, with particular attention given to a recently discovered opiate receptor, designated mu 3, with unique selectivity for morphine and certain other opiate alkaloids. Morphine, other opiate alkaloids and related analogs are known to bind to the classical delta, mu and kappa opioid receptor subtypes. Each of these subtypes also binds one or more of the endogenous opioid peptides with high affinity. Immunocytes have recently been found to contain a unique receptor for morphine, capable of binding morphine and certain other opiate alkaloids, but with essentially no or exceedingly low affinity for the naturally occurring endogenous opioid peptides or peptide analogs. This putative mu 3 (morphine/opiate alkaloid) receptor is present in invertebrate immunocytes as well as in human peripheral blood monocytes (macrophages). More recently this same receptor has been found in certain established macrophage cell lines and in human peripheral blood granulocytes. Finally, the same or closely related opiate alkaloid-selective (mu 3) receptor has been found to be present in a neuroblastoma and in a hybrid neural cell line. Studies indicate that in the immunocytes the receptor mediates inhibitory effects of morphine on cellular chemotaxis. While the functional coupling of this receptor in neurons is not known, it is postulated that the receptor may mediate effects of opiates on neuronal differentiation and cell division as well as neuronal transmission. Both for the immune system and the nervous system, the mu 3 receptor may constitute a major site of action for putative endogenous morphine or morphine-like substances. This receptor system also provides an additional pharmacological site of action for exogenously administered opiate alkaloid drugs. The mu 3 receptor is proposed to be an important neuro-immune link. This system is likely to play a significant role in a variety of responses involving the immune system, including the response of the organism to stress, infection and malignant transformation.
本文综述了吗啡的受体相互作用，特别关注最近发现的一种阿片受体，命名为μ3，它对吗啡和某些其他阿片生物碱具有独特的选择性。已知吗啡、其他阿片生物碱及相关类似物可与经典的δ、μ和κ阿片受体亚型结合。这些亚型中的每一种也能与一种或多种内源性阿片肽高亲和力结合。最近发现免疫细胞含有一种独特的吗啡受体，它能结合吗啡和某些其他阿片生物碱，但对天然存在的内源性阿片肽或肽类似物基本没有或亲和力极低。这种假定的μ3（吗啡/阿片生物碱）受体存在于无脊椎动物免疫细胞以及人类外周血单核细胞（巨噬细胞）中。最近，在某些已建立的巨噬细胞系和人类外周血粒细胞中也发现了相同的受体。最后，在一个神经母细胞瘤和一个杂交神经细胞系中也发现了相同或密切相关的阿片生物碱选择性（μ3）受体。研究表明，在免疫细胞中，该受体介导吗啡对细胞趋化性的抑制作用。虽然该受体在神经元中的功能偶联尚不清楚，但据推测该受体可能介导阿片类药物对神经元分化、细胞分裂以及神经传递的作用。对于免疫系统和神经系统而言，μ3受体可能构成假定的内源性吗啡或吗啡样物质的主要作用位点。该受体系统也为外源性给予的阿片生物碱药物提供了一个额外的药理作用位点。μ3受体被认为是一个重要的神经 - 免疫连接点。该系统可能在涉及免疫系统的多种反应中发挥重要作用，包括机体对应激、感染和恶性转化的反应。
