Role of cannabinoid CB1 receptors and tumor necrosis factor-α in the gut and systemic anti-inflammatory activity of SR 141716 (Rimonabant) in rodents
Article first published online: 30 JAN 2009
2003 British Pharmacological Society
British Journal of Pharmacology
Volume 140, Issue 1, pages 115–122, September 2003
How to Cite
Croci, T., Landi, M., Galzin, A.-M. and Marini, P. (2003), Role of cannabinoid CB1 receptors and tumor necrosis factor-α in the gut and systemic anti-inflammatory activity of SR 141716 (Rimonabant) in rodents. British Journal of Pharmacology, 140: 115–122. doi: 10.1038/sj.bjp.0705412
- Issue published online: 30 JAN 2009
- Article first published online: 30 JAN 2009
- (Received April 8, 2003, Revised May 7, 2003, Accepted June 12, 2003)
- CB1 receptor;
We investigated the effect of the cannabinoid CB1 receptor antagonist, SR 141716, on indomethacin-induced small intestine inflammation and Escherichia coli lipopolysaccharide (LPS)-induced plasma TNF-α (TNF) release in comparison to the cannabinoid CB2 receptor antagonist, SR 144528, in rodents.
In rats, indomethacin induced significant ulcer formation in the small intestine; this was accompanied by an increase in tissue TNF levels and myeloperoxidase (MPO) activity. SR 141716 prevented the ulcers and the rise in TNF levels (ID50 3.3, 0.4 mg kg−1, respectively) and MPO activity. SR 144528 prevented intestinal ulcers only.
The effect of SR 141716 against indomethacin-induced ulcers and increase of plasma TNF levels after LPS was also studied in wild-type and CB1 receptor knockout mice. Indomethacin induced intestinal ulcers in mice, but not tissue TNF production and MPO activity. SR 141716 reduced the ulcers to a similar extent in wild-type and CB1 receptor knockout mice. In rats and wild-type mice, but not in CB1 receptor knockout mice, SR 141716 inhibited the LPS-induced increase in plasma TNF levels.
These findings provide evidence that the indomethacin model of intestinal lesions differs in rat and mouse and support the existence of several mechanisms for the antiulcer activity of SR141716, the most important involving the inhibition of TNF production. The potent anti-inflammatory activity of SR141716 in rodents indicated its potential therapeutic interest in chronic immune-inflammatory diseases.
British Journal of Pharmacology (2003) 140, 115–122. doi:10.1038/sj.bjp.0705412