Komorowski Jan, Stepień Henryk
Klinika Endokrynologii Katedry Endokrynologii Uniwersytetu Medycznego w Łodzi, Łódź, Poland.
Postepy Hig Med Dosw (Online). 2007;61:99-105.
The endocannabinoid system has been recently recognized as an important modulatory system in the function of brain, endocrine, and immune tissues. It appears to play a very important regulatory role in the secretion of hormones related to reproductive functions and response to stress. The important elements of this system are: endocannabinoid receptors (types CB1 and CB2), their endogenous ligands (N-arachidonoylethanolamide, 2-arachidonoyl glycerol), enzymes involved in their synthesis and degradation, as well as cannabinoid antagonists. In humans this system also controls energy homeostasis and mainly influences the function of the food intake centers of the central nervous system and gastrointestinal tract activity. The endocannabinoid system regulates not only the central and peripheral mechanisms of food intake, but also lipids synthesis and turnover in the liver and adipose tissue as well as glucose metabolism in muscle cells. Rimonabant, a new and selective central and peripheral cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factor (metabolic syndrome) in obese patients by increasing HDL-cholesterol and adiponectin blood levels as well as decreasing LDL-cholesterol, leptin, and C-reactive protein (a proinflammatory marker) concentrations. It is therefore possible to speculate about a future clinical use of CB1 antagonists, as a means of improving gonadotrophin pulsatility and fertilization capacity as well as the prevention of cardiovasculary disease and type 2 diabetes mellitus. Drugs acting as agonists of CB1 receptors (Dronabinol, Dexanabinol) are currently proposed for evaluation as drugs to treat neurodegenerative disorders (Alzheimer's and Parkinson's diseases), epilepsy, anxiety, and stroke.
内源性大麻素系统最近被认为是大脑、内分泌和免疫组织功能中的一个重要调节系统。它似乎在与生殖功能相关的激素分泌和应激反应中发挥着非常重要的调节作用。该系统的重要组成部分包括:内源性大麻素受体(CB1和CB2型)、它们的内源性配体(N-花生四烯酰乙醇胺、2-花生四烯酰甘油)、参与其合成和降解的酶以及大麻素拮抗剂。在人类中,该系统还控制能量平衡,主要影响中枢神经系统食物摄入中心的功能和胃肠道活动。内源性大麻素系统不仅调节食物摄入的中枢和外周机制,还调节肝脏和脂肪组织中的脂质合成和周转以及肌肉细胞中的葡萄糖代谢。利莫那班是一种新型选择性中枢和外周大麻素-1受体(CB1)阻滞剂,已被证明可通过提高高密度脂蛋白胆固醇和脂联素的血液水平以及降低低密度脂蛋白胆固醇、瘦素和C反应蛋白(一种促炎标志物)的浓度来减轻肥胖患者的体重并改善心血管危险因素(代谢综合征)。因此,可以推测CB1拮抗剂未来的临床用途,作为改善促性腺激素脉冲性和受精能力以及预防心血管疾病和2型糖尿病的一种手段。目前有人提议将作为CB1受体激动剂的药物(屈大麻酚、右大麻酚)作为治疗神经退行性疾病(阿尔茨海默病和帕金森病)、癫痫、焦虑和中风的药物进行评估。