Carriba Paulina, Ortiz Oskar, Patkar Kshitij, Justinova Zuzana, Stroik Jessica, Themann Andrea, Müller Christa, Woods Anima S, Hope Bruce T, Ciruela Francisco, Casadó Vicent, Canela Enric I, Lluis Carme, Goldberg Steven R, Moratalla Rosario, Franco Rafael, Ferré Sergi
Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
Neuropsychopharmacology. 2007 Nov;32(11):2249-59. doi: 10.1038/sj.npp.1301375. Epub 2007 Mar 14.
The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB1 receptors, is still a matter of debate. In the present study, we report that CB1 and adenosine A2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB1 receptor signaling was found to be completely dependent on A2A receptor activation. Accordingly, blockade of A2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A2A and CB1 receptors.
大麻素通过中枢表达的大麻素CB1受体发挥运动抑制作用的作用机制仍存在争议。在本研究中，我们报告CB1和腺苷A2A受体在共转染的HEK-293T细胞和大鼠纹状体中形成异聚体复合物，它们在纤维状结构中共定位。在人神经母细胞瘤细胞系中，发现CB1受体信号传导完全依赖于A2A受体激活。因此，阻断A2A受体可抵消纹状体内注射大麻素CB1受体激动剂所产生的运动抑制作用。这些生化和行为学发现表明，大麻素的显著运动效应取决于纹状体A2A和CB1受体之间的物理和功能相互作用。
