A Cannabinoid-1 Receptor Antagonist MJ08 with Different Effects in Stomach and Small Intestine.

Background

To investigate the inverse agonistic effect of a novel type 1 cannabinoid (CB1) receptor antagonist, MJ08, on the gastrointestinal tract (GIT).

Methods

In vivo, carbon propulsion within the stomach of mice was undertaken to investigate the effects of MJ08. In vitro, the effects of MJ08 were investigated on the contraction of smooth muscle on the isolated gastric fundus, gastric body, duodenum, jejunum, and ileum.

Results

Western blotting results showed that MJ08 (0.62 mg/kg body weight) reversed WIN55,212-2 (1.0 mg/kg)-induced reduction of carbon transit. MJ08 (1.25, 2.5 mg/kg) stimulated carbon transit dose dependently, demonstrating an inverse agonistic effect. In vitro experiments showed that the expression of MJ08 increased the contraction of small intestine, and that its inverse agonistic effect was significantly stronger than that of SR141716A, but no effect was noted on the gastric body. Western blotting showed that the MJ08 increased the expression of CB1 receptor in different GIT segments.

Conclusion

MJ08 is not only an antagonist but also an inverse agonist of the CB1 receptor. MJ08 and SR141716A can enhance motility in the small intestine and increase the expression of CB1 receptor in the small intestine.