Goldberger Esty, Tauber Merav, Ben-Chaim Yair
Department of Natural and Life Sciences, The Open University of Israel, Ra'anana, Israel.
Front Pharmacol. 2022 Oct 11;13:1022275. doi: 10.3389/fphar.2022.1022275. eCollection 2022.
Cannabinoids produce their characteristic effects mainly by binding to two types of G-protein coupled receptors (GPCRs), the CB1 and CB2 cannabinoid receptors. The CB1 receptor is the main cannabinoid receptor in the central nervous system, and it participates in many brain functions. Recent studies showed that membrane potential may serve as a novel modulatory modality of many GPCRs. Here, we used oocytes as an expression system to examine whether membrane potential modulates the activity of the CB1 receptor. We found that the potencies of the endocannabinoid 2-AG and the phytocannabinoid THC in activating the receptor are voltage dependent; depolarization enhanced the potency of these agonists and decreased their dissociation from the receptor. This voltage dependence appears to be agonist dependent as the potency of the endocannabinoid anandamide (AEA) was voltage independent. The finding of this agonist-specific modulatory factor for the CB1 receptor may contribute to our future understanding of various physiological functions mediated by the endocannabinoid system.
大麻素主要通过与两种类型的G蛋白偶联受体（GPCRs），即CB1和CB2大麻素受体结合来产生其特征性作用。CB1受体是中枢神经系统中的主要大麻素受体，它参与许多脑功能。最近的研究表明，膜电位可能作为许多GPCRs的一种新型调节方式。在这里，我们使用卵母细胞作为表达系统来研究膜电位是否调节CB1受体的活性。我们发现内源性大麻素2-AG和植物大麻素THC激活该受体的效力是电压依赖性的；去极化增强了这些激动剂的效力并减少了它们从受体上的解离。这种电压依赖性似乎是激动剂依赖性的，因为内源性大麻素花生四烯乙醇胺（AEA）的效力是电压非依赖性的。CB1受体这种激动剂特异性调节因子的发现可能有助于我们未来对内源性大麻素系统介导的各种生理功能的理解。
