uroguanylin and Adenocarcinoma
uroguanylin has been researched along with Adenocarcinoma* in 2 studies
Other Studies
2 other study(ies) available for uroguanylin and Adenocarcinoma
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Gastrointestinal pain: unraveling a novel endogenous pathway through uroguanylin/guanylate cyclase-C/cGMP activation.
The natural hormone uroguanylin regulates intestinal fluid homeostasis and bowel function through activation of guanylate cyclase-C (GC-C), resulting in increased intracellular cyclic guanosine-3',5'-monophosphate (cGMP). We report the effects of uroguanylin-mediated activation of the GC-C/cGMP pathway in vitro on extracellular cGMP transport and in vivo in rat models of inflammation- and stress-induced visceral hypersensitivity. In vitro exposure of intestinal Caco-2 cells to uroguanylin stimulated bidirectional, active extracellular transport of cGMP into luminal and basolateral spaces. cGMP transport was significantly and concentration dependently decreased by probenecid, an inhibitor of cGMP efflux pumps. In ex vivo Ussing chamber assays, uroguanylin stimulated cGMP secretion from the basolateral side of rat colonic epithelium into the submucosal space. In a rat model of trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, orally administered uroguanylin increased colonic thresholds required to elicit abdominal contractions in response to colorectal distension (CRD). Oral administration of cGMP mimicked the antihyperalgesic effects of uroguanylin, significantly decreasing TNBS- and restraint stress-induced visceromotor response to graded CRD in rats. The antihyperalgesic effects of cGMP were not associated with increased colonic spasmolytic activity, but were linked to significantly decreased firing rates of TNBS-sensitized colonic afferents in rats in response to mechanical stimuli. In conclusion, these data suggest that the continuous activation of the GC-C/cGMP pathway along the intestinal tract by the endogenous hormones guanylin and uroguanylin results in significant reduction of gastrointestinal pain. Extracellular cGMP produced on activation of GC-C is the primary mediator in this process via modulation of sensory afferent activity. Topics: Acetylcholine; Acetylglucosamine; Adenocarcinoma; Animals; Cell Differentiation; Cell Line, Tumor; Colitis; Colon; Colorectal Neoplasms; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Female; Gastrointestinal Diseases; Gene Expression Regulation, Neoplastic; Guanylate Cyclase; Humans; Hyperalgesia; Intestinal Mucosa; Male; Mast Cells; Morphine; Multidrug Resistance-Associated Proteins; Natriuretic Peptides; Organic Anion Transporters, Sodium-Independent; Peroxidase; Rats; Rats, Sprague-Dawley; Rats, Wistar; Restraint, Physical; RNA, Messenger; Signal Transduction; Trinitrobenzenesulfonic Acid; Visceral Pain | 2013 |
Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP.
The enteric peptides, guanylin and uroguanylin, are local regulators of intestinal secretion by activation of receptor-guanylate cyclase (R-GC) signaling molecules that produce cyclic GMP (cGMP) and stimulate the cystic fibrosis transmembrane conductance regulator-dependent secretion of Cl- and HCO3-. Our experiments demonstrate that mRNA transcripts for guanylin and uroguanylin are markedly reduced in colon polyps and adenocarcinomas. In contrast, a specific uroguanylin-R-GC, R-GCC, is expressed in polyps and adenocarcinomas at levels comparable with normal colon mucosa. Activation of R-GCC by uroguanylin in vitro inhibits the proliferation of T84 colon cells and elicits profound apoptosis in human colon cancer cells, T84. Therefore, down-regulation of gene expression and loss of the peptides may interfere with renewal and/or removal of the epithelial cells resulting in the formation of polyps, which can progress to malignant cancers of the colon and rectum. Oral replacement therapy with human uroguanylin was used to evaluate its effects on the formation of intestinal polyps in the Min/+ mouse model for colorectal cancer. Uroguanylin significantly reduces the number of polyps found in the intestine of Min/+ mice by approximately 50% of control. Our findings suggest that uroguanylin and guanylin regulate the turnover of epithelial cells within the intestinal mucosa via activation of a cGMP signaling mechanism that elicits apoptosis of target enterocytes. The intestinal R-GC signaling molecules for guanylin regulatory peptides are promising targets for prevention and/or therapeutic treatment of intestinal polyps and cancers by oral administration of human uroguanylin. Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Aged; Aged, 80 and over; Amino Acid Sequence; Animals; Apoptosis; Caco-2 Cells; Colonic Neoplasms; Cyclic GMP; Down-Regulation; Female; Gastrointestinal Hormones; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Molecular Sequence Data; Natriuretic Peptides; Peptides; Receptors, Cell Surface; RNA, Messenger; Tumor Cells, Cultured | 2000 |