Endocannabinoid system: An overview of its potential in current medical practice.
Endocannabinoid system: An overview of its potential in current medical practice.
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内源性大麻素系统：概述其在当前医疗实践中的潜力。
DOI：
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
V. Valla
中科院分区：
文献类型：
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作者：
Z. Mouslech;V. Valla
内源性大麻素系统（ECS）是一种脂质信号传导系统，由内源性大麻素样配体（内源性大麻素）花生四烯酸（AEA）和2-花生四烯酸甘油（2-AG）组成。它们与一个称为CB 1和CB 2的G蛋白偶联受体家族结合。大麻素受体1（CB 1 R）分布在与运动控制，情绪反应，动机行为和能量稳态相关的大脑区域。在外周，相同的受体在脂肪组织、胰腺、肝脏、胃肠道、骨骼肌、心脏和生殖系统中表达。CB 2 R主要在免疫系统中表达，调节其功能。内源性大麻素以受体依赖性方式按需合成和释放。它们在GABA能和突触能突触中作为逆行信号信使，并作为突触后传递的调节剂，与其他神经递质相互作用。内源性大麻素通过特定的摄取系统转运到细胞中，并被脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）降解。ECS参与中枢和外周组织中的各种病理生理条件。它涉及食物摄入、心血管、胃肠道、免疫、行为、抗增殖和哺乳动物生殖功能的激素调节。最近的进展表明ECS与药物成瘾和酒精中毒有关。越来越多的ECS调节剂的临床前和临床数据必然会导致目前治疗不足的许多疾病的新的治疗方法。ECS的失调与肥胖和代谢综合征的发病机制有关。利莫那班是第一个用于治疗肥胖和超重患者心脏代谢危险因素的CB 1阻滞剂。III期临床试验表明，该药物能够调节腹腔内脂肪组织水平，血糖，血糖和炎症参数。然而，安全问题导致了它的退出。内源性大麻素在哺乳动物生殖中的作用是一个新兴的研究领域，因为它们在受精、植入前胚胎和精子发生中具有重要意义。内源性大麻素信号的相关临床前数据开辟了新的视角，作为改善人类不育和生殖健康的目标。
The endocannabinoid system (ECS) is a lipid signalling system, comprising of the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which derive from arachidonic acid. These bind to a family of G-protein-coupled receptors, called CB1 and CB2. The cannabinoid receptor 1 (CB1R) is distributed in brain areas associated with motor control, emotional responses, motivated behaviour and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, pancreas, liver, GI tract, skeletal muscles, heart and the reproduction system. The CB2R is mainly expressed in the immune system regulating its functions. Endocannabinoids are synthesized and released upon demand in a receptor-dependent way. They act as retrograde signalling messengers in GABAergic and glutamatergic synapses and as modulators of postsynaptic transmission, interacting with other neurotransmitters. Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS is involved in various pathophysiological conditions in central and peripheral tissues. It is implicated in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immune, behavioral, antiproliferative and mammalian reproduction functions. Recent advances have correlated the ECS with drug addiction and alcoholism. The growing number of preclinical and clinical data on ECS modulators is bound to result in novel therapeutic approaches for a number of diseases currently treated inadequately. The ECS dysregulation has been correlated to obesity and metabolic syndrome pathogenesis. Rimonabant is the first CB1 blocker launched to treat cardiometabolic risk factors in obese and overweight patients. Phase III clinical trials showed the drug's ability to regulate intra-abdominal fat tissue levels, lipidemic, glycemic and inflammatory parameters. However, safety conerns have led to its withrawal. The role of endocannabinoids in mammalian reproduction is an emerging research area given their implication in fertilization, preimplantation embryo and spermatogenesis. The relevant preclinical data on endocannabinoid signalling open up new perspectives as a target to improve infertility and reproductive health in humans.