Kirkham T C, Tucci S A
School of Psychology, University of Liverpool, Eleanor Rathbone Building, Bedford Street South, Liverpool L69 7ZA, UK.
CNS Neurol Disord Drug Targets. 2006 Jun;5(3):272-92. doi: 10.2174/187152706777452272.
Research into the endocannabinoid 'system' has grown exponentially in recent years, with the discovery of cannabinoid receptors and their endogenous ligands, such as anandamide and 2-arachidonoylglycerol (2-AG). Important advances have been made in our understanding of endocannabinoid transduction mechanisms, their metabolic pathways, and of the biological processes in which they are implicated. A decade of endocannabinoid studies has promoted new insights into neural regulation and mammalian physiology that are as revolutionary as those arising from the discovery of the endogenous opioid peptides in the 1970s. Thus, endocannabinoids have been found to act as retrograde signals: released by postsynaptic neurons, they bind to presynaptic heteroceptors to modulate the release of inhibitory and excitatory neurotransmitters through multiple G-protein-coupled receptor (GPCR)-linked effector mechanisms. The metabolic pathways of anandamide and 2-AG have now been been characterised in great detail, and we can anticipate that these pathways -- together with endocannabinoid uptake mechanisms -- will complement cannabinoid receptors as targets for the pharmacological analysis of the physiological functions of these substances. Specific insights into the potential role of endocannabinoid-CB1 receptor systems in central appetite control, peripheral metabolism and body weight regulation herald the clinical application of CB1 receptor antagonists in the management of obesity and its associated disorders.
近年来，随着大麻素受体及其内源性配体如花生四烯酸乙醇胺和2-花生四烯酸甘油酯（2-AG）的发现，对内源性大麻素“系统”的研究呈指数级增长。我们对内源性大麻素转导机制、其代谢途径以及它们所涉及的生物学过程的理解取得了重要进展。十年的内源性大麻素研究催生了对神经调节和哺乳动物生理学的新见解，这些见解与20世纪70年代发现内源性阿片肽时产生的见解一样具有革命性。因此，内源性大麻素已被发现可作为逆行信号：由突触后神经元释放，它们与突触前异源受体结合，通过多种G蛋白偶联受体（GPCR）相关的效应机制调节抑制性和兴奋性神经递质的释放。花生四烯酸乙醇胺和2-AG的代谢途径现已得到详细表征，我们可以预期，这些途径——连同内源性大麻素摄取机制——将作为这些物质生理功能药理分析的靶点，与大麻素受体相辅相成。对内源性大麻素-CB1受体系统在中枢食欲控制、外周代谢和体重调节中的潜在作用的具体见解预示着CB1受体拮抗剂在肥胖及其相关疾病管理中的临床应用。
