The Function of 5‐HT₃ Receptors on Colonic Transit in Rats

Abstract

Ondansetron (10 mgkg, p.0.) and granisetron (1 mgkg, p.0.) also inhibited the stress-accelerated colonic transit, but azasetron was more effective than these two drugs. Atropine methylbromide (0.1 mg/kg, s .~) and tetrodotoxin (0.01 mg/kg, s.c.) inhibited the accelerated colonic transit under stress conditions, but methysergide (10 mgkg, s.c.), SDZ205-557 (10 mg/kg, s.c.), domperidone (30 mgkg, P.o.), trimebutine (300 mgkg, P.o.), and metoclopramide (30 mgkg, p.0.) did not. Azasetron (10 pg) administered intracerebroventricularly did not inhibit the stressinduced acceleration. These results suggest that endogenous 5-HT which is released through stress accelerates the colonic transit via the 5-HT3 receptors and finally a cholinergic mechanism. It is considered that azasetron inhibits colonic transit partic- ularly under stress conditions through the blockade of the peripheral 5-HT3 receptors. Azasetron may improve bowel function in strewrelated colonic dysfunction like irritable bowel syndrome.

Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats

“…Whereas the systemic administration of 5-HT has been shown to accelerate colonic transit in rats (13), the effects of intraluminal application of 5-HT were previously unknown. In our study, intraluminal administration of 5-HT into the proximal colon significantly increased the fecal pellet output and accelerated colonic transit.…”

“…There are significantly fewer 5-HT-immunoreactive cells in patients with chronic slow-transit constipation (7). Colonic transit is accelerated by 5-HT in conscious rats (13,16); this effect is inhibited by a selective 5-HT 3 receptor antagonist (13). A selective 5-HT 3 receptor antagonist also slowed colonic transit in healthy men (30).…”

Mast cells are required for experimental oral allergen–induced diarrhea

“…Effect of different antiallergic drug treatments on diarrhea net fluid secretion induced by cholera toxin (25) and colonic transit in rats (45). Interestingly, diarrhea in patients with irritable bowel syndrome is improved by treatment with alosetron, a 5-HT 3 antagonist (46).…”

Effect of psychogenic stress on gastrointestinal function

“…Serotonin participates also in motility disturbances in the colon brought about by stress or CRH mainly via activation of 5-HT 3 receptors located distal to a cholinergic pathway (61,117,204,205). In addition, serotonin receptors are involved in stressevoked defaecation (1,76).…”