期刊
NEUROPSYCHOPHARMACOLOGY
卷 32, 期 11, 页码 2249-2259出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1301375
关键词
adenosine A(2A) receptor; cannabinoid CB1 receptor; receptor heteromerization; striatum; cyclic AMP; motor activity
资金
- Intramural NIH HHS Funding Source: Medline
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 A(2A) 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 A(2A) receptor activation. Accordingly, blockade of A(2A) 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 A(2A) and CB1 receptors.
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