Brown Andrew J, Robin Hiley C
Department of Screening and Compound Profiling, Molecular Discovery Research, GlaxoSmithKline, New Frontiers Science Park, GlaxoSmithKline, Essex, UK.
Vitam Horm. 2009;81:111-37. doi: 10.1016/S0083-6729(09)81005-4.
Anandamide activates CB(1) cannabinoid receptors but also has effects, particularly in the vasculature, that cannot be explained by actions at either this or the other cloned cannabinoid receptor, the CB(2) receptor. These effects are probably mediated by a novel G protein-coupled receptor, but genome searching has not revealed a strong candidate. Several approaches have suggested that an orphan receptor, GPR55, is a target for anandamide, but the pharmacology of this receptor is such that it cannot be categorically identified as a cannabinoid receptor. GPR55 appears primarily to be a receptor for lysophosphatidylinositol which may exhibit biased agonism, leading to it also responding to anandamide. GPR55 activates G(alpha12) and G(alpha13) and thence RhoA, leading to an oscillatory intracellular Ca(2+) signal. Further complexity arises from possible interactions between the anandamide-sensitive CB(1) receptor and GPR55. Overall, it appears that GPR55 has several signaling modalities and that, while anandamide can activate systems containing this receptor, GPR55 cannot yet be primarily designated a receptor for this endocannabinoid.
花生四烯乙醇胺可激活CB(1)大麻素受体，但它也有一些作用，特别是在脉管系统中，这些作用无法用其对该受体或另一种克隆的大麻素受体CB(2)受体的作用来解释。这些作用可能是由一种新型G蛋白偶联受体介导的，但基因组搜索尚未发现强有力的候选受体。几种方法表明，孤儿受体GPR55是花生四烯乙醇胺的一个靶点，但该受体的药理学特性使其不能被明确归类为大麻素受体。GPR55似乎主要是溶血磷脂酰肌醇的受体，溶血磷脂酰肌醇可能表现出偏向性激动作用，从而导致它也对花生四烯乙醇胺产生反应。GPR55激活G(α12)和G(α13)，进而激活RhoA，导致细胞内Ca(2+)信号振荡。花生四烯乙醇胺敏感的CB(1)受体与GPR55之间可能存在的相互作用进一步增加了复杂性。总体而言，似乎GPR55具有多种信号传导方式，虽然花生四烯乙醇胺可以激活含有该受体的系统，但GPR55目前还不能被主要指定为这种内源性大麻素的受体。
