Identification and Functional Characterization of Brainstem Cannabinoid CB2 Receptors
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.
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We thank L. Oland, W. Ho, and N. Shariat for excellent technical support and animal care. Q.J.P., J.S.D., and K.A.S. were supported by the Canadian Institutes of Health Research (CIHR); K.D.P. by a CIHR group grant in leukocyte trafficking; L.J.M. by GM15431; and K.M., N.S., A.M., and D.P. by U.S. National Institutes of Health. M.D.V.S. is an Alberta Heritage Foundation for Medical Research (AHFMR) graduate student; M.D. is an AHFMR and Canadian Association of Gastroenterology/CIHR/Janssen-Ortho postdoctoral fellow; K.D.P. holds a Canada research chair and is an AHFMR senior scholar; and Q.J.P. and K.A.S. are AHFMR medical scientists.
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Published In
Science
Volume 310 | Issue 5746
14 October 2005
14 October 2005
Copyright
American Association for the Advancement of Science.
Submission history
Received: 6 June 2005
Accepted: 9 September 2005
Published in print: 14 October 2005
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www.sciencemag.org/cgi/content/full/310/5746/329/DC1
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- Marja D. Van Sickle et al.
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Identification of peripheral cannabinoid receptors in the central nervous system
The recent report by Van Sickle et al. on the identification and functional characterization of brainstem cannabinoid CB2 receptors in the brainstem (14 Oct. 2005, p. 329) is consistent, in part, with other recent reports of brain CB2 receptor expression. However, this report appears to understate the more widespread and multifocal functional CB2 distribution that we and others have reported.
Cannabinoid CB2 receptors have been termed "peripheral," since they were initially cloned from immune cells. Such observations have prompted investigators to seek and identify CB2 receptors in populations of immune -derived brain microglial cells. The report by Van Sickle et al. is an important contribution in understanding CB2 receptors in specific brainstem locations and documenting their possible functional significance. However, we are concerned that the focus on brainstem localizations and antiemetic functions may understate the importance of CB2 receptors in the other brain areas in which we and others have identified CB2 mRNA and protein.