ORIGINAL ARTICLE Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB 1 and CB 2 receptors Martin A. Storr & Catherine M. Keenan & Dominik Emmerdinger & Hong Zhang & Birol Yüce & Andrei Sibaev & Federico Massa & Nancy E. Buckley & Beat Lutz & Burkhard Göke & Stephan Brand & Kamala D. Patel & Keith A. Sharkey Received: 18 January 2008 / Revised: 31 March 2008 / Accepted: 3 April 2008 / Published online: 21 May 2008 # Springer-Verlag 2008 Abstract 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 J Mol Med (2008) 86:925–936 DOI 10.1007/s00109-008-0359-6 M. A. Storr (*) Division of Gastroenterology, Department of Medicine, University of Calgary, 3280 Hospital Dr. N.W., Calgary, Alberta T2N 4N1, Canada e-mail: mstorr@ucalgary.ca M. A. Storr : C. M. Keenan : H. Zhang : K. D. Patel : K. A. Sharkey Institute of Infection, Immunity and Inflammation and Hotchkiss Brain Institute, Department of Physiology & Biophysics, University of Calgary, 3280 Hospital Dr. N.W., Calgary, Alberta T2N 4N1, Canada M. A. Storr : D. Emmerdinger : B. Yüce : A. Sibaev : B. Göke : S. Brand Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377 Munich, Germany F. Massa INSERM, Inst. F. Magendi, Avenir 146 Rue Leo Saignat, 33077 Bordeaux, France MARTIN A. STORR received his M.D. from the Technical University of Munich, Germany, with a thesis in Experimental Gastroenterology. He is presently an Associate Professor of Gastroenterology at the Department of Medicine at the University of Calgary, Canada. His research interests include translational research in the field of Neurogastroenterol- ogy with a focus on the role of the endocannabinoid, endoopioid and endovanilloid systems in the physiology and pathophysiology of the digestive tract. KEITH A. SHARKEY received his Ph.D. in Physiology from the University of Liver- pool, UK. He is presently Pro- fessor of Physiology & Biophysics, an Alberta Heritage Foundation for Medical Re- search Medical Scientist and the Crohn’ s and Colitis Foundation of Canada Chair in Inflammato- ry Bowel Disease Research at the University of Calgary, Alberta, Canada. His research interests include investigations of the neural control of the gastrointestinal (GI) tract in health and inflammatory condi- tions and the role of endocan- nabinoids in GI tract and brain–gut axis.