Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated. To further clarify the underlying mechanism, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the 5-HT depleting agent parachlorophenylalanine (pCPA) were applied to adjust serum levels of 5-HT. Serum levels of 5-HT were measured using LC-MS/MS; the expression of hepatic transporters, DMEs, and nuclear receptors were examined by Western-blot technique. Our results showed that in PI-IBS rats the expression of multidrug resistance protein 2 (Mrp2) was significantly decreased, while colonic enterochromaffin cell density and serum levels of 5-HT were all significantly increased. Moreover, 5-HTP treatment significantly increased serum levels of 5-HT and decreased the expression of Mrp2 and glycoprotein P (P-gp), whereas treatment with pCPA markedly decreased serum levels of 5-HT and increased the expression of Mrp2 and P-gp. Our results indicated that serum 5-HT regulates the expression of Mrp2 and P-gp, and the underlying mechanism may be related to the altered expression of the nuclear receptor constitutive androstane receptor (CAR).
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PMID:Serum serotonin reduced the expression of hepatic transporter Mrp2 and P-gp via regulating nuclear receptor CAR in PI-IBS rats. 2605 41

Bile acids modulate several gastrointestinal functions including electrolyte secretion and absorption, gastric emptying, and small intestinal and colonic motility. High concentrations of bile acids lead to diarrhea and are implicated in the development of esophageal, gastric and colonic cancer. Alterations in bile acid homeostasis are also implicated in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Our understanding of the mechanisms underlying these effects of bile acids on gut functions has been greatly enhanced by the discovery of bile acid receptors, including the nuclear receptors: farnesoid X receptor (FXR), vitamin D receptor (VDR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR); and the G protein-coupled receptors: Takeda G protein-coupled receptor (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and muscarinic acetylcholine receptor M3 (M3R).. For example, various studies provided evidence demonstrating the anti-inflammatory effects FXR and TGR5 activation in models of intestinal inflammation. In addition, TGR5 activation in enteric neurons was recently shown to increase colonic motility, which may lead to bile acid-induced diarrhea. Interestingly, TGR5 induces the secretion of glucagon-like peptide-1 (GLP-1) from L-cells to enhance insulin secretion and modulate glucose metabolism. Because of the importance of these receptors, agonists of TGR5 and intestine-specific FXR agonists are currently being tested as an option for the treatment of diabetes mellitus and primary bile acid diarrhea, respectively. This review summarizes current knowledge of the functional roles of bile acid receptors in the gastrointestinal tract.
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PMID:Bile Acid Receptors and Gastrointestinal Functions. 3236 58