Tolerance to cannabinoid response on the myenteric plexus of guinea-pig ileum and human small intestinal strips
Article first published online: 29 JAN 2009
2006 British Pharmacological Society
British Journal of Pharmacology
Volume 148, Issue 8, pages 1165–1173, August 2006
How to Cite
Guagnini, F., Cogliati, P., Mukenge, S., Ferla, G. and Croci, T. (2006), Tolerance to cannabinoid response on the myenteric plexus of guinea-pig ileum and human small intestinal strips. British Journal of Pharmacology, 148: 1165–1173. doi: 10.1038/sj.bjp.0706813
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received April 5, 2006, Revised May 3, 2006, Accepted May 12, 2006)
- CB1 receptors;
- (+)WIN 55,212-2;
- human small intestine;
- guinea-pig small intestine;
- 1We studied tolerance to cannabinoid agonist action by comparing the in vitro inhibition of electrically evoked contractions of longitudinal muscle from small intestine of human and guinea-pig (myenteric plexus preparations) after 48-h incubation with the synthetic agonist (+) WIN 55,212-2. We also investigated the intrinsic response to the selective cannabinoid CB1 receptor antagonist rimonabant in control and tolerant strips.
- 2(+) WIN 55,212-2 inhibited guinea-pig (IC50 4.8 nM) and human small intestine (56 nM) contractions with similar potency before or after 48-h incubation in drug-free conditions; this effect was competitively antagonized by rimonabant (pA2, 8.4, 8.2). A 48-h preincubation with (+) WIN 55,212-2, but not with (−) WIN 55,212-3, completely abolished the acute agonist response in both tissue preparations. The opiate K-receptor agonist U69593 inhibited human small intestine contractions with a similar potency in control and strips tolerant to (+) WIN 55,212-2, IC50 39 and 43 nM.
- 3Unlike human tissue, in guinea-pig small intestine, which has a high level of endocannabinoids, rimonabant alone increased the twitches induced by the electrical field stimulation (EC50 100 nM) with a maximal effect of 123%.
- 4In strips tolerant to (+) WIN 55,212-2, rimonabant markedly increased (155%) the electrical twitches in human ileum and in guinea-pig myenteric plexus smooth muscle (133%).
- 5This study shows tolerance can be induced to the cannabinoids' action in intestinal strips of human and guinea-pig by long in vitro incubation with the agonist (+) WIN 55,212-2.
British Journal of Pharmacology (2006) 148, 1165–1173. doi:10.1038/sj.bjp.0706813