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 Γ=ΓΓ 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 Γ=Γ 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 Γ=Γ 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.