Colorectal Distention and Intraluminal Cholera Toxin Induce Propulsive Contractions Through 5 HT3 Receptors on Pelvic-nerve Afferents in Decerebrated Rats
It is well known that 5-hydroxytriptamine-3 (5-HT3) receptor antagonists prevent nausea and vomiting caused by the release of 5-HT from enterochromaffin cells in patients treated with chemical or radiation therapy for cancer, and that these antagonists produce constipation. Consistently, 5-HT3 receptor agonists have been reported to alleviate constipation. These antagonists prevent the binding of 5-HT to receptors on abdominal vagal afferents, and thus produce an antiemetic effect. These findings suggest that the defecation reflex may be induced by 5-HT released from enterochromaffin cells. This study was planned to examine this possibility in decerebrate rats. Since intestinal distention and intraluminal cholera toxin have been reported to release 5-HT from the intestinal wall, we used both stimuli to stimulate enterochromaffin cells. Intraluminal infusion of cholera toxin (0.2 mg in 1 ml saline) enhanced colorectal propulsive contractions, and this enhancement was significantly attenuated by i.v. application of the 5-HT3 receptor antagonist granisetron, and also by bilateral severance of the pelvic nerve. Colorectal contractions in response to colorectal distension were also significantly inhibited by both treatments. These results are consistent with the assumption noted above and suggest that cholera toxin and colorectal distension induce the defecation reflex through the activation of colorectal pelvic- nerve afferents via 5-HT3 receptors and 5-TH released from enterochromaffin cells.