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)

Based on analysis of aligned amino acid sequences the following statements are made: (i) There is evolutionary homology between the N-terminal extracellular region of ionotropic Glutamate receptors/Kainate Binding Proteins and a family of procaryote amino acid binding proteins. (ii) Homology of the N-terminal extracellular domain of the metabotropic glutamate receptors with a family of receptors with a guanylate cyclase intracellular domain appears to be valid. (iii) There is no evidence for homology between the N-terminal extracellular domain of the nicotinic Acetylcholine, GABA, Glycine and 5HT3 receptors and that of the ionotropic Glutamate receptors/Kainate Binding proteins. (iv) The proposal of homology for the N-terminal extracellular domain of metabotropic Glutamate receptors and that of ionotropic Glutamate receptors does not appear to hold.
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PMID:Homologies and disparities of glutamate receptors: a critical analysis. 828 Nov 27

The relaxations mediated by the activation of 5-HT receptors in the guinea pig proximal colon were investigated. Longitudinal strips were cut from the colon segment and placed into the bath. In the presence of atropine (0.2 microM), the relaxations were evoked by adding increasing concentrations of 5-HT (1-100 microM). Noncumulative concentration-response curves were established in the absence and presence of either 5-HT or nitric oxide synthase (NOS) antagonists. Selective 5-HT3 antagonists tropisetron (10 and 100 nM) and ondansetron (1 microM) inhibited the relaxations and shifted the concentration-response curves to the right. Similar effects were observed in the presence of the NOS inhibitor N(G)-nitro-L-arginine (3.2, 10, 32 microM) and partly reversed with L-arginine (100, 320 microM). N(G)-nitro-D-arginine, serving as a negative control, was ineffective. The relaxations were further inhibited in the presence of the soluble guanylate cyclase blocker methylene blue (10 microM) or NO scavenger hemoglobin (32 microM). These results suggest that the 5-HT3 receptor plays a role in neurogenic relaxations of guinea pig proximal colon, which are at least partly mediated via release of NO from nerve endings.
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PMID:Is nitric oxide involved in 5-HT3 receptor-mediated neurogenic relaxation of guinea pig proximal colon? 974 26

Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.
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PMID:Treatment of abdominal pain in irritable bowel syndrome. 2484 49

In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation. For IBS with diarrhea (IBS-D), the 5-HT3 receptor antagonist ramosetron showed efficacy in men and women, but is currently only approved in Japan. A multicenter study with the anti-emetic 5-HT3 receptor antagonist ondansetron showed efficacy on stool pattern in IBS-D. The poorly absorbable antibiotic rifaximin and eluxadoline, a mu opioid receptor agonist and delta antagonist, both showed efficacy in phase III trials in IBS-D and were approved by the FDA. Eluxadoline was associated with increased occurrence of sphincter of Oddi spasm and biliary pancreatitis. The non-pharmacological treatment of IBS, with dietary interventions (mainly gluten elimination and low FODMAP (fructose, oligo-, di-, monosaccharides and polyols)) has received a lot of attention lately. While responder rates vary across studies, perhaps based on regional variations in dietary intake of FODMAPs, the dietary approach seems to have acquired recognition as a valid therapeutic alternative. Long-term studies and comparative studies with pharmacotherapy, as well as elucidation of the underlying mechanisms of action, are needed.
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PMID:Modern Management of Irritable Bowel Syndrome: More Than Motility. 2733 17