Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Spain.
Neuropharmacology and Pain Group, Neuroscience Program, Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Spain.
Acta Neuropsychiatr. 2024 Oct;36(5):320-324. doi: 10.1017/neu.2023.30. Epub 2023 Aug 22.
Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A receptors (ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of AR.
We used HEK-293T cells transfected with the cDNA encoding the human AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on AR ligand binding using an AR NanoLuciferase sensor. Next, we evaluated whether CBD modified AR coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on AR intrinsic activity by recording agonist-induced cAMP accumulation.
CBD did not bind orthosterically to AR but reduced the coupling of AR to Gαs protein and the subsequent generation of cAMP.
CBD negatively modulates AR functioning.
大麻二酚（CBD）是一种具有巨大临床应用潜力的植物大麻素。其作用机制尚需进一步研究。先前的研究表明，腺苷 A 受体（AR）可能在 CBD 诱导作用中发挥作用。在此，我们评估了 CBD 调节 AR 功能的能力。
我们使用转染了编码人 AR 和 Gαs 蛋白 cDNA 的 HEK-293T 细胞进行了实验，这两种蛋白均经过修饰以进行基于生物发光的测定。我们首先使用 AR NanoLuciferase 传感器评估了 CBD 对 AR 配体结合的影响。接下来，我们使用 NanoBiT™ 测定法评估了 CBD 是否改变了 AR 与 mini-Gαs 蛋白的偶联。最后，我们通过记录激动剂诱导的 cAMP 积累，进一步评估了 CBD 对 AR 内在活性的影响。
CBD 没有与 AR 进行正位结合，但降低了 AR 与 Gαs 蛋白的偶联，以及随后 cAMP 的产生。
CBD 负调节 AR 功能。
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