Oddi Sergio, Spagnuolo Paola, Bari Monica, D'Agostino Antonella, Maccarrone Mauro
Department of Biomedical Sciences, University of Teramo, Teramo 64100, Italy.
Int Rev Neurobiol. 2007;82:327-37. doi: 10.1016/S0074-7742(07)82017-4.
Endocannabinoid-signaling chains have been implicated in a variety of pathophysiological functions, including memory, coordination, vasoregulation, reproduction, neurodegeneration, and inflammation. These activities were thought to be mediated by the activation of two G-protein-coupled receptors (GPCRs), type 1 and type 2 cannabinoid receptors (CB(1)R and CB(2)R). These two CBR subtypes share common agonists and trigger similar signaling pathways, yet they present several important differences in structure and cell distribution. In particular, recent research has shown that the CB(1)R and CB(2)R are differentially linked to lipid rafts, specialized microdomains of the plasma membrane involved in the signaling of many other GPCRs. We present an overview of the current literature on the effects that lipid raft perturbation have on CBRs activities, and provide a mechanistic model to interpret these data in terms of structural and functional aspects. These findings may also have important implications for the development of new therapeutic approaches, including lipid raft perturbing drugs, aimed to selectively modulate CB(1)R signaling in a variety of pathological conditions.
内源性大麻素信号传导通路已被证明参与多种病理生理功能，包括记忆、协调、血管调节、生殖、神经退行性变和炎症。这些活动被认为是由两种G蛋白偶联受体（GPCR），即1型和2型大麻素受体（CB(1)R和CB(2)R）的激活介导的。这两种CBR亚型具有共同的激动剂并触发相似的信号通路，但它们在结构和细胞分布上存在一些重要差异。特别是，最近的研究表明，CB(1)R和CB(2)R与脂筏有不同的联系，脂筏是质膜的特殊微区，参与许多其他GPCR的信号传导。我们概述了当前关于脂筏扰动对CBR活性影响的文献，并提供了一个机制模型，从结构和功能方面解释这些数据。这些发现可能对新治疗方法的开发也具有重要意义，包括旨在在各种病理条件下选择性调节CB(1)R信号传导的脂筏扰动药物。
