Balenga Nariman A B, Henstridge Christopher M, Kargl Julia, Waldhoer Maria
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
Adv Pharmacol. 2011;62:251-77. doi: 10.1016/B978-0-12-385952-5.00004-X.
According to The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), ∼70 million European adults have consumed cannabis on at least one occasion. Cannabis consumption leads to a variety of psychoactive effects due to the presence of the constituent Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC interacts with the endocannabinoid system (ECS), which consists of the seven transmembrane spanning (7TM)/G protein-coupled receptors (GPCRs) CB(1) and CB(2), their respective ligands (endocannabinoids), and enzymes involved in their biosynthesis and degradation. This system plays a critical role in many physiological processes such as learning and memory, appetite control, pain sensation, motor coordination, lipogenesis, modulation of immune response, and the regulation of bone mass. Therefore, a huge effort has been spent trying to fully elucidate the composition and function of the ECS. The G protein-coupled receptor 55 (GPR55) was recently proposed as a novel component of this system; however, its classification as a cannabinoid receptor has been significantly hampered by its complex pharmacology, signaling, and cellular function. GPR55 is phylogenetically distinct from the traditional cannabinoid receptors, but in some experimental paradigms, it is activated by endocannabinoids, phytocannabinoids, and synthetic cannabinoid ligands. However, the most potent compound appears to be a lysophospholipid known as lysophosphatidylinositol (LPI). Here, we provide a comprehensive evaluation of the current pharmacology and signaling of GPR55 and review the proposed role of this receptor in a number of physiological and pathophysiological processes.
据欧洲药物和药物成瘾监测中心（EMCDDA）称，约7000万欧洲成年人至少有过一次大麻消费经历。由于大麻成分Δ(9)-四氢大麻酚（Δ(9)-THC）的存在，大麻消费会导致多种精神活性作用。Δ(9)-THC与内源性大麻素系统（ECS）相互作用，该系统由七个跨膜（7TM）/G蛋白偶联受体（GPCR）CB(1)和CB(2)、它们各自的配体（内源性大麻素）以及参与其生物合成和降解的酶组成。该系统在许多生理过程中发挥着关键作用，如学习和记忆、食欲控制、痛觉、运动协调、脂肪生成、免疫反应调节以及骨量调节。因此，人们花费了巨大努力试图全面阐明ECS的组成和功能。G蛋白偶联受体55（GPR55）最近被提议作为该系统的一个新成分；然而，其作为大麻素受体的分类因复杂的药理学、信号传导和细胞功能而受到严重阻碍。GPR55在系统发育上与传统大麻素受体不同，但在一些实验范式中，它可被内源性大麻素、植物大麻素和合成大麻素配体激活。然而，最有效的化合物似乎是一种称为溶血磷脂酰肌醇（LPI）的溶血磷脂。在此，我们对GPR55当前的药理学和信号传导进行全面评估，并综述该受体在一些生理和病理生理过程中所提出的作用。
