Evidence for a cannabinoid receptor in immunomodulation by cannabinoid compounds.
Evidence for a cannabinoid receptor in immunomodulation by cannabinoid compounds.
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大麻素化合物免疫调节中大麻素受体的证据。
DOI：
10.1007/978-1-4615-2980-4_16
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发表时间：
1993
影响因子：
--
通讯作者：
Kaminski,NE
中科院分区：
文献类型：
--
作者：
Kaminski,NE
许多结构上相关的大麻类化合物，包括大麻的主要精神活性成分--三角洲-9-四氢大麻酚(Δ9-THC)，已被广泛证实具有免疫抑制作用。虽然关于哪些免疫反应对大麻素的调节表现出敏感性已经了解了很多，但造成这些影响的机制(S)仍然不清楚。在过去的十年里，关于大麻素对中枢神经系统(CNS)影响的细胞和生化机制方面的重大见解即将到来。从这些研究中，至少出现了三条证据，有力地暗示了大麻素受体在中枢神经系统大麻素活性中的作用，包括：(1)立体选择性效应；(2)合成的双环大麻素CP-55,940与各种脑组织制备的高度特异性结合，通过放射性配基结合分析；(3)大麻素对腺苷酸环化酶-cAMP第二信使系统的调节。松田及其同事(1)最近通过从大鼠脑cDNA文库中分离和克隆G蛋白偶联受体，证实了与神经元组织相关的大麻素受体的存在。当克隆时，该受体表现出推测的大麻素受体的所有特征。最近，从人脑中克隆了一种几乎相同的受体，它与松田及其同事分离的受体具有97%以上的同源性。根据这些发现，目前报道的研究的目的是探索模拟大麻药物的免疫抑制是通过免疫细胞上存在的大麻素受体介导的可能性。
A number of structurally related cannabinoid compounds, including the major psychoactive component of marihuana, delta-9-tetrahydrocannabinol (Δ9-THC), have been widely established as being immunosuppressive. Although much has been learned with respect to which immune responses demonstrate sensitivity to modulation by cannabinoids, the mechanism(s) responsible for these effects has remained elusive. Over the past decade, significant insight has been forthcoming regarding the cellular and biochemical mechanisms which mediate the effects of cannabinoids on the central nervous system (CNS). From these investigations at least three lines of evidence have emerged which strongly implicated a role by a cannabinoid receptor in CNS association cannabinoid activity and include: (i) stereoselective effects; (ii) a high degree of specific binding by the synthetic bicyclic cannabinoid, CP-55,940, to various brain tissue preparation as analyzed by radioligand binding; and (iii) cannabinoid modulation of adenylate cyclase-cAMP second messenger system. The existence of a cannabinoid receptor in association with neuronal tissue has been recently confirmed by Matsuda and coworkers (1) through the isolation and cloning of a G-protein coupled receptor from a rat brain cDNA library. When cloned, this receptor demonstrate all of the characteristics predicted for a putative cannabinoid receptor. More recently, an almost identical receptor has been cloned from human brain which possessed more than 97% homogeneity (2) to that isolated by Matsuda and coworkers. In light of these findings, the objective of the presently reported studies was to explore the possibility that immune inhibition by cannabimimetic agents is mediated through a cannabinoid receptor present on immunocytes.