Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the possible involvement of 5-HT3 receptors in the colonic motor alterations and abdominal pain evoked by rectal distension (RD) in rats, under normal and inflammatory conditions. Responses to RD were evaluated by electromyography in rats treated with 5-HT3 antagonists (ondansetron and cilansetron, 0.1 and 1 mg/kg, intraperitoneally), before and 3 days after intrarectal administration of TNB/ethanol. RD evoked a significant (P < 0.05) and gradual inhibition of the occurrence of colonic spike bursts (SB) and a gradual increase in abdominal SB from 11 mm in diameter on wards. Ondansetron and cilansetron (0.1 mg/kg) significantly reduced both the colonic (62 and 66%, respectively) and the abdominal response (28 and 61%, respectively) for an 11 mm diameter of RD. After TNB/ethanol, both colonic and abdominal responses to RD were significantly (P < 0.05) enhanced and appeared for a lower diameter (9 mm) (colon: 4.8 +/- 0.9 vs 8.4 +/- 1.1, abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4). Cilansetron (0.1, 1 mg/kg) significantly (P < 0.05) attenuated the TNB-induced colonic motor inhibition, while ondansetron and cilansetron (0.1, 1 mg/kg) reduced the TNB-induced increase in abdominal response. We conclude that 5-HT and 5-HT3 receptors mediate RD-induced viscerosensitive alterations in rats, both in normal conditions and during TNB-induced rectocolitis. However, the relative efficacy of the 5-HT3 receptor antagonists depends on the experimental conditions (intact or inflamed bowel) and does not appear to increase with the dose.
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PMID:Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats. 772 Dec 33

Serotonin and 5-HT3 receptors may be involved in the activation of nociceptive afferent pathways by rectal distension. In rats, intracolonic infusion of glycerol is able to trigger nociceptive inputs as evidenced by the occurrence of abdominal constrictions. This work was designed to evaluate the influence of 5-HT3 receptor antagonists on this reflex and to approach the site of action by comparing their relative efficacies according to the route of administration. Male Wistar rats (250-350 g) were surgically prepared for abdominal electromyography and a catheter was placed in the colonic lumen. Five days after surgery, electrical activity of abdominal muscles was recorded before and during (20 min) intracolonic infusion of glycerol (60% glycerol + 40% saline, rate 0.75 mL/h). Cilansetron was administered intraperitoneally, 15 min before glycerol infusion, at doses of 5 to 500 micrograms/kg. Granisetron, ondansetron and cilansetron were administered at the dose of 20 micrograms/kg by intraperitoneal (i.p.), intravenous (i.v.) or intracolonic (i.c.) routes. The number of abdominal spike bursts was used as an index of visceral nociception. Intracolonic infusion of glycerol increased significantly (P < 0.05) the number of abdominal spike bursts during the time of infusion compared with saline (30.6 +/- 6.6 vs 4.5 +/- 3.4 bursts). When administered i.p., cilansetron dose-dependently reduced the frequency of abdominal spike bursts from the dose of 20 micrograms/kg i.p. Administration i.p. of granisetron and ondansetron at this dose also significantly reduced the number of abdominal spikes (19.0 +/- 6.0 and 18.3 +/- 6.9 respectively). Cilansetron, ondansetron and granisetron were also effective by i.v. and i.c. routes, cilansetron was more active by the i.c. route. Serotonin, via 5-HT3 receptors, is involved in the mediation of abdominal contractions induced by intracolonic infusion of glycerol. 5-HT3 receptor antagonists are also active by i.c. route suggesting a local site of action.
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PMID:Intracolonic glycerol induces abdominal contractions in rats: role of 5-HT3 receptors. 981 94

The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory refl exes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.
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PMID:Serotonin receptor modulators in the treatment of irritable bowel syndrome. 1872 19