gastrins and Colitis

This study investigates the effects of Uliveto, a bicarbonate-alkaline mineral water, in experimental models of diarrhea, constipation and colitis. Rats were allowed to drink Uliveto or oligomineral water (control) for 30 days. Diarrhea and constipation were evoked by 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) or loperamide, respectively. Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) or acetic acid. Gastric emptying, small-intestinal and colonic transit were evaluated. dmPGE(2)-induced diarrhea reduced gastric emptying and increased small-intestinal and colonic transit. In this setting, Uliveto water enhanced gastric emptying, and this effect was prevented by L-365,260 (gastrin receptor antagonist). Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic transit, and these effects were prevented by Uliveto water. L-365,260 counteracted the effects of Uliveto on gastric emptying, while alosetron (serotonin 5-HT(3) receptor antagonist) blunted the effect of Uliveto on colonic transit. Gastric emptying, small-intestinal and colonic transit were reduced in DNBS-induced colitis, and Uliveto water enhanced gastric emptying and normalized small-intestinal and colonic transit. Gastric emptying, small-intestinal and colonic transit were also reduced in acetic acid-induced colitis, and Uliveto increased both gastric emptying and small-intestinal transit. In conclusion, Uliveto water exerts beneficial effects on gastrointestinal motility in the presence of bowel motor dysfunctions. The effects of Uliveto water on gastric emptying depend on gastrin-mediated mechanisms, whereas the activation of serotonergic pathways accounts for the modulation of colonic functions.

Topics: Animals; Benzodiazepinones; Bicarbonates; Colitis; Constipation; Diarrhea; Disease Models, Animal; Gastric Emptying; Gastrins; Gastrointestinal Motility; Hydrogen-Ion Concentration; Male; Mineral Waters; Phenylurea Compounds; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT3

Resistin and resistin-like molecule (RELM)beta comprise a novel class of cysteine-rich proteins secreted into the circulation implicated in hepatic insulin resistance and inflammation. RELMbeta is specifically produced by intestinal goblet cells but regulation of its expression and much of its local function are not elucidated. RELMbeta has been suggested to regulate colonic inflammation susceptibility, which is dependent on the mucosal barrier integrity.. In this work we explored the physiopathological role of RELMbeta in the colon. Among agents tested, carbachol and gastrin were strong inhibitors of RELMbeta mRNA accumulation. We examined the effect of recombinant RELMbeta on mucin secretion by human mucus-secreting HT29-Cl.16E cells in culture and by mouse colonic goblet cells in vivo.. RELMbeta upregulated MUC2 and M1/MUC5AC gene expression in HT29-Cl.16E cells. RELMbeta enhanced M1/MUC5AC secretion by human colonic HT29-Cl.16E cells and MUC2 secretion by murine intestinal goblet cells. RELMbeta exerted its action exclusively on the apical side of HT29-Cl.16E cells, in agreement with its luminal mucosecretagogue effect in mice. Its action required calcium, protein kinase C, tyrosine kinases, and extracellular-regulated protein kinase activities and was synergized by carbachol. An intracolonic RELMbeta challenge was performed in the trinitrobenzene sulfonic acid (TNBS)-murine model of colitis and macroscopic and histological scores were monitored. The macroscopic and histopathological severity of TNBS-induced colitis was significantly attenuated by RELMbeta pretreatment.. A direct participation in maintaining the mucosal defense barrier can be ascribed to RELMbeta in line with a regulatory role in intestinal inflammation.

Topics: Animals; Blotting, Western; Calcium; Carbachol; Cells, Cultured; Colitis; Gastrins; Gene Expression; Goblet Cells; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Intestines; Mice; Mucin 5AC; Mucin-2; Mucins; Mucus; Protein Kinase C; Protein Kinases; Protein-Tyrosine Kinases; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Trinitrobenzenesulfonic Acid

A number of growth factors affect the regeneration of intestinal epithelia following injury, but the effects of amidated gastrin have not previously been assessed. We therefore investigated the effects of gastrin on intestinal regeneration following a range of stimuli.. Intestinal crypt regeneration was assessed in transgenic mice overexpressing amidated gastrin (INS-GAS) and mice in which hypergastrinemia was induced using omeprazole, following gamma-radiation, 5-fluorouracil, and dextran sulphate sodium (DSS). Abundance of the CCK-2 receptor was assessed in intestinal epithelia and IEC-6 intestinal epithelial cells following gamma-radiation.. Four days following 14 Gy gamma-radiation, or 2 injections of 400 mg/kg 5-fluorouracil, INS-GAS mice exhibited significantly increased small intestinal and colonic crypt survival compared with their wild-type counterparts (FVB/N). INS-GAS mice treated with 3% DSS for 5 days showed less weight loss and increased colonic crypt regeneration at 8 days compared with FVB/N. Increased small intestinal and colonic crypt survival was also demonstrated following gamma-radiation in FVB/N mice rendered hypergastrinemic using omeprazole. The increased crypt survival in INS-GAS mice following 14 Gy gamma-radiation was inhibited by administration of a CCK-2 receptor antagonist (YF476). Increased abundance of the CCK-2 receptor was demonstrated in intestinal epithelia following 14 Gy gamma-radiation by Western blotting and immunohistochemistry. Similarly, increased CCK-2 receptor mRNA abundance and increased 125I-gastrin binding was demonstrated in IEC-6 cells following 4 Gy gamma-radiation.. Hypergastrinemia increases regeneration of intestinal epithelia following diverse forms of injury. Induction of the CCK-2 receptor in damaged epithelium confers potential for protection against injury by administration of gastrin.

Topics: Animals; Benzodiazepinones; Cell Line; Cell Proliferation; Colitis; Dextran Sulfate; Enteritis; Enzyme Inhibitors; Fluorouracil; Gamma Rays; Gastrins; Growth Substances; Intestinal Mucosa; Mice; Mice, Inbred Strains; Mice, Transgenic; Omeprazole; Phenylurea Compounds; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Regeneration; Wounds and Injuries

Topics: Adult; Colitis; Enteritis; Female; Gastrins; Growth Hormone; Humans; Hydrocortisone; Insulin; Male