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Identification and Functional Characterization of Brainstem Cannabinoid CB2 Receptors
Marja D. Van Sickle,1*Marnie Duncan,1*Philip J. Kingsley,2Abdeslam Mouihate,1Paolo Urbani,3Ken Mackie,4Nephi Stella,5Alexandros Makriyannis,6Daniele Piomelli,7Joseph S. Davison,1Lawrence J. Marnett,2Vincenzo Di Marzo,3Quentin J. Pittman,1Kamala D. Patel,1Keith A. Sharkey1
The presence and function of CB2 receptors in central nervoussystem (CNS) neurons are controversial. We report the expressionof CB2 receptor messenger RNA and protein localization on brainstemneurons. These functional CB2 receptors in the brainstem wereactivated by a CB2 receptor agonist, 2-arachidonoylglycerol,and by elevated endogenous levels of endocannabinoids, whichalso act at CB1 receptors. CB2 receptors represent an alternativesite of action of endocannabinoids that opens the possibilityof nonpsychotropic therapeutic interventions using enhancedendocannabinoid levels in localized brain areas.
1 Institute of Infection, Immunity, and Inflammation and Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada T2N 4N1. 2 Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 372320146, USA. 3 Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy. 4 Department of Anesthesiology and Department of Physiology and Biophysics, University of Washington, Seattle, WA 981956540, USA. 5 Department of Pharmacology, Psychiatry, and Behavioral Sciences, University of Washington, Seattle, WA 981957280, USA. 6 Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA. 7 Department of Pharmacology, Gillespie Neuroscience Facility, University of California, Irvine, CA 926976180, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: ksharkey{at}ucalgary.ca
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