大麻二酚能负向调节活细胞中腺苷 A2A 受体的功能。

IF 3.8 4区医学 Q1 Medicine

Acta Neuropsychiatrica Pub Date : 2024-10-01 Epub Date: 2023-08-22 DOI:10.1017/neu.2023.30

Nuria Sánchez-Fernández, Laura Gómez-Acero, Laura I Sarasola, Josep Argerich, Andy Chevigné, Kenneth A Jacobson, Francisco Ciruela, Víctor Fernández-Dueñas, Ester Aso

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引用次数: 0

摘要

目的：大麻二酚（CBD）是一种具有巨大临床应用潜力的植物大麻素。大麻二酚的作用机制需要进一步研究。以前的研究表明，腺苷 A2A 受体（A2ARs）可能在 CBD 诱导的效应中发挥作用。在此，我们评估了 CBD 改变 A2AR 功能的能力：我们使用转染了编码人类 A2AR 和 Gαs 蛋白的 cDNA 的 HEK-293T 细胞，这两种细胞都经过修饰，可以进行基于生物发光的检测。我们首先使用 A2AR 纳米荧光素酶传感器评估了 CBD 对 A2AR 配体结合的影响。接着，我们使用 NanoBiT™ 检测法评估了 CBD 是否改变了 A2AR 与 mini-Gαs 蛋白的耦合。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 A2AR 内在活性的影响：结果：CBD 没有与 A2AR 正交结合，但减少了 A2AR 与 Gαs 蛋白的耦合以及随后产生的 cAMP：结论：CBD 负向调节 A2AR 的功能。

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Cannabidiol negatively modulates adenosine A_2A receptor functioning in living cells.

Objectives: 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_2A receptors (A_2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A_2AR.

Methods: We used HEK-293T cells transfected with the cDNA encoding the human A_2AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A_2AR ligand binding using an A_2AR NanoLuciferase sensor. Next, we evaluated whether CBD modified A_2AR coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on A_2AR intrinsic activity by recording agonist-induced cAMP accumulation.

Results: CBD did not bind orthosterically to A_2AR but reduced the coupling of A_2AR to Gαs protein and the subsequent generation of cAMP.

Conclusion: CBD negatively modulates A_2AR functioning.

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来源期刊

Acta Neuropsychiatrica 医学-精神病学

CiteScore

8.50

自引率

5.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.