Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors.
J Mol Med. 2008-05-21; 86(8): 925-936
DOI: 10.1007/s00109-008-0359-6
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1. J Mol Med (Berl). 2008 Aug;86(8):925-36. doi: 10.1007/s00109-008-0359-6. Epub
2008 May 21.
Targeting endocannabinoid degradation protects against experimental colitis in
mice: involvement of CB1 and CB2 receptors.
Storr MA(1), Keenan CM, Emmerdinger D, Zhang H, Yüce B, Sibaev A, Massa F,
Buckley NE, Lutz B, Göke B, Brand S, Patel KD, Sharkey KA.
Author information:
(1)Division of Gastroenterology, Department of Medicine, University of Calgary,
Calgary, Alberta, Canada.
The endocannabinoid (EC) system mediates protection against intestinal
inflammation. In this study, we investigated the effects of blocking EC
degradation or cellular reuptake in experimental colitis in mice. Mice were
treated with trinitrobenzene-sulfonic acid in presence and absence of the fatty
acid amide hydrolase (FAAH) blocker URB597, the EC membrane transport inhibitor
VDM11, and combinations of both. Inflammation was significantly reduced in the
presence of URB597, VDM11, or both as evaluated by macroscopic damage score,
myeloperoxidase levels, and colon length. These effects were abolished in CB(1)-
and CB(2)-receptor-gene-deficient mice. Quantitative reverse transcription
polymerase chain reaction after induction of experimental colitis by different
pathways showed that expression of FAAH messenger RNA (mRNA) is significantly
reduced in different models of inflammation early in the expression of colitis,
and these return to control levels as the disease progresses. Genomic DNA from
202 patients with Crohn’s disease (CD) and 206 healthy controls was analyzed for
the C385A polymorphism in the FAAH gene to address a possible role in humans. In
our groups, the C385A polymorphism was equally distributed in patients with CD
and healthy controls. In conclusion, drugs targeting EC degradation offer
therapeutic potential in the treatment of inflammatory bowel diseases.
Furthermore, reduction of FAAH mRNA expression is involved in the
pathophysiological response to colitis.
DOI: 10.1007/s00109-008-0359-6
PMID: 18493729 [Indexed for MEDLINE]