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Endocannabinoids in Appetite Control and the Treatment of Obesity

机译:内源性大麻素在食欲控制和肥胖症的治疗中

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摘要

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.
机译:近年来,随着大麻素受体及其内源性配体(如花生四烯酸酰胺和2-花生四烯酸甘油酯(2-AG))的发现,对大麻素“系统”的研究呈指数增长。我们对内源性大麻素的转导机制,它们的代谢途径以及涉及它们的生物学过程的理解已取得重要进展。十年来的内源性大麻素研究促进了神经调节和哺乳动物生理学方面的新见解,这些见解与1970年代发现内源性阿片样肽所产生的见解一样具有革命性。因此,已发现内源性大麻素起逆行信号的作用:由突触后神经元释放,它们与突触前异受体结合,通过多种G蛋白偶联受体(GPCR)连锁的效应子机制调节抑制性和兴奋性神经递质的释放。现在已对anandamide和2-AG的代谢途径进行了详细描述,我们可以预期这些途径以及内源性大麻素摄取机制将补充大麻素受体,作为这些物质生理功能的药理分析的靶标。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潜在作用的具体见解预示了CB1受体拮抗剂在肥胖症及其相关疾病管理中的临床应用。

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