Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats

Wood creosote has been used as an herbal medicine against acute diarrhea caused by food poisoning and has an inhibitory effect on colonic motility and enterotoxin-induced ion secretion. Since no previous studies have examined the effects of wood creosote on stress-induced alteration of colonic motility, we examined the effects on the colonic motility altered by intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key mediator in responses to stress. We recorded motor activity in proximal and distal colon of unrestrained conscious rats via two manometory catheters. The frequencies of phase III-like contraction and the % motor indices in both proximal and distal colon were measured. At the same time the number of fecal pellets excreted was counted. I.c.v. injection of CRF increased the motor activity in both proximal and distal colon, and these effects were completely antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed by intravenously administered wood creosote. Intraluminal administration of the 5-HT3 receptor antagonist granisetron, or the 5-HT4 receptor antagonist SB 204070 blocked the increase in colonic motility induced by i.c.v. injection of CRF. Wood creosote prevented the increase in colonic motility induced by the 5-HT3 receptor agonist SR57227A in the proximal colon, while it prevented the increase in colonic motility induced by the 5-HT4 receptor agonist RS67506 in the distal colon. These results indicate that wood creosote prevents the increase in colonic motility induced by CRF via 5-HT3 receptors in the proximal colon, and via 5-HT4 receptors in the distal colon, suggesting that wood creosote might be useful to treat stress-induced diarrhea.