Cannabinoid activation of peroxisome proliferator-activated receptors: Potential for modulation of inflammatory disease
Cannabinoid activation of peroxisome proliferator-activated receptors: Potential for modulation of inflammatory disease
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DOI：
10.1016/j.imbio.2009.09.007
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发表时间：
2010-08-01
期刊：
影响因子：
2.8
通讯作者：
Kendall, D. A.
中科院分区：
文献类型：
--
作者：
O'Sullivan, S. E.;Kendall, D. A.
大麻素通过细胞表面G蛋白偶联受体（CB 1和CB 2）和离子通道受体TRPV 1发挥作用。现在已经出现的证据表明，另一个目标是过氧化物酶体增殖物激活受体（PPAR）家族的核受体。有三种PPAR亚型α，δ（也称为β）和γ，它们调节细胞分化，代谢和免疫功能。主要的内源性大麻素，花生四烯酸和2-花生四烯酸甘油，以及阿佳酸，植物大麻素δ（9）-四氢大麻酚（THC）的结构类似物，具有由PPAR γ介导的抗炎特性。其他激活PPAR γ的大麻素包括N-花生四烯酸-多巴胺、THC、大麻二酚、HU 210、WIN 55212 -2和CP 55940。内源性酰基乙醇胺、油酰乙醇胺和棕榈酰乙醇胺调节进食和体重，刺激脂肪利用，并具有通过PPAR α介导的神经保护作用。其他激活PPAR α的内源性大麻素包括大麻素、virodhamine和noladin ether。到目前为止，大麻素与PPAR δ相互作用的直接证据很少。大麻素通过细胞表面和核受体对免疫细胞功能起作用，其对免疫细胞功能的作用是趋同的，这为各种免疫疾病，特别是神经炎性疾病的靶向治疗提供了希望。(C)2009年Elsevier GmbH。All rights reserved.
Cannabinoids act via cell surface G protein-coupled receptors (CB1 and CB2) and the ion channel receptor TRPV1. Evidence has now emerged suggesting that an additional target is the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors. There are three PPAR subtypes alpha, delta (also known as beta) and gamma, which regulate cell differentiation, metabolism and immune function. The major endocannabinoids, anandamide and 2-arachidonoylglycerol, and ajulemic acid, a structural analogue of the phytocannabinoid Delta(9)-tetrahydrocannabinol (THC), have anti-inflammatory properties mediated by PPAR gamma. Other cannabinoids which activate PPAR gamma include N-arachidonoyl-dopamine, THC, cannabidiol, HU210, WIN55212-2 and CP55940. The endogenous acylethanolamines, oleoylethanolamide and palmitoylethanolamide regulate feeding and body weight, stimulate fat utilization and have neuroprotective effects mediated through PPAR alpha. Other endocannabinoids that activate PPAR alpha include anandamide, virodhamine and noladin ether. There is, as yet, little direct evidence for interactions of cannabinoids with PPAR delta. There is a convergence of effects of cannabinoids, acting via cell surface and nuclear receptors, on immune cell function which provides promise for the targeted therapy of a variety of immune, particularly neuroinflammatory, diseases. (C) 2009 Elsevier GmbH. All rights reserved.