Navarro Gemma, Varani Katia, Reyes-Resina Irene, Sánchez de Medina Verónica, Rivas-Santisteban Rafael, Sánchez-Carnerero Callado Carolina, Vincenzi Fabrizio, Casano Salvatore, Ferreiro-Vera Carlos, Canela Enric I, Borea Pier Andrea, Nadal Xavier, Franco Rafael
Department of Biochemistry and Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red, Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
Front Pharmacol. 2018 Jun 21;9:632. doi: 10.3389/fphar.2018.00632. eCollection 2018.
Cannabigerol (CBG) is one of the major phytocannabinoids present in L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB (CBR) and CB (CBR) receptors and the effects of the compound on agonist activation of those receptors and of CB-CB heteroreceptor complexes. Using [H]-CP-55940, CBG competed with low micromolar values the binding to CBR and CBR. Homogeneous binding in living cells, which is only technically possible for the CBR, provided a 152 nM value. Also interesting, CBG competed the binding of [H]-WIN-55,212-2 to CBR but not to CBR (: 2.7 versus >30 μM). The phytocannabinoid modulated signaling mediated by receptors and receptor heteromers even at low concentrations of 0.1-1 μM. cAMP, pERK, β-arrestin recruitment and label-free assays in HEK-293T cells expressing the receptors and treated with endocannabinoids or selective agonists proved that CBG is a partial agonist of CBR. The action on cells expressing heteromers was similar to that obtained in cells expressing the CBR. The effect of CBG on CBR was measurable but the underlying molecular mechanisms remain uncertain. The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.
大麻二酚（CBG）是大麻中存在的主要植物大麻素之一，因其无精神活性且在某些工业大麻品种中含量丰富而引起了药理学关注。这项工作的目的是同时研究CBG与大麻素CB1（CB1R）和CB2（CB2R）受体的结合特性，以及该化合物对这些受体和CB1-CB2异源受体复合物激动剂激活的影响。使用[3H]-CP-55940，CBG以低微摩尔浓度与CB1R和CB2R的结合竞争。活细胞中的均相结合（仅对CB1R在技术上可行）给出了152 nM的值。同样有趣的是，CBG竞争[3H]-WIN-55,212-2与CB1R的结合，但不与CB2R结合（IC50：2.7对>30 μM）。即使在0.1-1 μM的低浓度下，这种植物大麻素也能调节由CB1R和受体异聚体介导的信号传导。在表达这些受体并用内源性大麻素或选择性激动剂处理的HEK-293T细胞中进行的cAMP、pERK、β-抑制蛋白募集和无标记测定证明，CBG是CB1R的部分激动剂。对表达异聚体的细胞的作用与在表达CB1R的细胞中获得的作用相似。CBG对CB2R的作用是可测量的，但其潜在的分子机制仍不确定。结果表明，CBG确实作为内源性大麻素信号的调节剂有效。
