Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil
Article first published online: 30 JAN 2009
2000 British Pharmacological Society
British Journal of Pharmacology
Volume 129, Issue 8, pages 1627–1632, April 2000
How to Cite
Izzo, A. A., Pinto, L., Borrelli, F., Capasso, R., Mascolo, N. and Capasso, F. (2000), Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil. British Journal of Pharmacology, 129: 1627–1632. doi: 10.1038/sj.bjp.0703265
- Issue published online: 30 JAN 2009
- Article first published online: 30 JAN 2009
- (Received December 2, 1999, Revised January 25, 2000, Accepted January 28, 2000)
- Intestinal motility;
- cannabinoid receptors;
- inflammatory bowel disease;
- antidiarrhoeal drugs;
- small intestine
We have evaluated the effect of cannabinoid drugs, administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) on upper gastrointestinal transit in control and in croton oil-treated mice.
The cannabinoid agonists, WIN 55,212-2 (2–239 nmol mouse−1) and cannabinol (24–4027 nmol mouse−1), decreased while the CB1 antagonist SR141716A (2–539 nmol mouse−1) increased transit in control mice. WIN 55,212-2, cannabinol and SR141716A had lower ED50 values when administered i.c.v., than when administered i.p. The CB2 antagonist SR144528 (52 nmol mouse−1, i.p.) was without effect.
During croton oil (0.01 ml mouse−1, p.o.)-induced diarrhoea, the ED50 values of i.p.-injected WIN 55,212-2 and cannabinol (but not SR141716A) were significantly decreased (compared to control mice). However, the ED50 values of WIN 55,212-2 were similar after i.p. or i.c.v. administration.
The inhibitory effects of WIN 55,212-2 and cannabinol were counteracted by SR141716A (16 nmol mouse−1, i.p.) but not by SR144528 (52 nmol mouse−1, i.p.) both in control and croton-oil treated mice.
Ganglionic blockade with hexamethonium (69 nmol mouse−1, i.p.) did not modify the inhibitory effect of i.p.-injected cannabinoid agonists either in control or in croton-oil treated mice.
The lower ED50 values of cannabinoid drugs after i.c.v. administration suggest a central (CB1) site of action. However, a peripheral site of action is suggested by the lack of effect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the effect of cannabinoid agonists by a peripheral mechanism.
British Journal of Pharmacology (2000) 129, 1627–1632; doi:10.1038/sj.bjp.0703265