Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis.
BACKGROUND
Activation of cannabinoid (CB)(1) receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB(2) receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB(2) receptor-deficient (CB(2) (-/-)) mice.


METHODS
Mice were treated with TNBS to induce colitis and then given intraperitoneal injections of the CB(2) receptor agonists JWH133, AM1241, or the CB(2) receptor antagonist AM630. Additionally, CB(2) (-/-) mice were treated with TNBS and injected with JWH133 or AM1241. Animals were examined 3 days after the induction of colitis. The colons were removed for macroscopic and microscopic evaluation, as well as the determination of myeloperoxidase activity. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for CB(2) receptor was also performed in animals with TNBS and dextran sodium sulfate colitis.


RESULTS
Intracolonic installation of TNBS caused severe colitis. CB(2) mRNA expression was significantly increased during the course of experimental colitis. Three-day treatment with JWH133 or AM1241 significantly reduced colitis; AM630 exacerbated colitis. The effect of JWH133 was abolished when animals were pretreated with AM630. Neither JWH133 nor AM1241 had effects in CB(2) (-/-) mice.


CONCLUSIONS
We show that activation of the CB(2) receptor protects against experimental colitis in mice. Increased expression of CB(2) receptor mRNA and aggravation of colitis by AM630 suggests a role for this receptor in normally limiting the development of colitis. These results support the idea that the CB(2) receptor may be a possible novel therapeutic target in inflammatory bowel disease.
Storr
Martin A
MA
Division of Gastroenterology, Department of Medicine and Snyder Institute of Infection, Immunity & Inflammation, University Calgary, Calgary, Alberta, Canada. mstorr@ucalgary.ca
Keenan
Catherine M
CM
Zhang
Hong
H
Patel
Kamala D
KD
Makriyannis
Alexandros
A
Sharkey
Keith A
KA
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics
C439263:AM 1241; D002186:Cannabinoids; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline