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Science 310 (5746): 329-332

Copyright © 2005 by the American Association for the Advancement of Science

Identification and Functional Characterization of Brainstem Cannabinoid CB2 Receptors

Marja D. Van Sickle,1* Marnie Duncan,1* Philip J. Kingsley,2 Abdeslam Mouihate,1 Paolo Urbani,3 Ken Mackie,4 Nephi Stella,5 Alexandros Makriyannis,6 Daniele Piomelli,7 Joseph S. Davison,1 Lawrence J. Marnett,2 Vincenzo Di Marzo,3 Quentin J. Pittman,1 Kamala D. Patel,1 Keith A. Sharkey1{dagger}

Abstract: The presence and function of CB2 receptors in central nervous system (CNS) neurons are controversial. We report the expression of CB2 receptor messenger RNA and protein localization on brainstem neurons. These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors. CB2 receptors represent an alternative site of action of endocannabinoids that opens the possibility of nonpsychotropic therapeutic interventions using enhanced endocannabinoid 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 37232–0146, 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 98195–6540, USA.
5 Department of Pharmacology, Psychiatry, and Behavioral Sciences, University of Washington, Seattle, WA 98195–7280, 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 92697–6180, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ksharkey{at}ucalgary.ca

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