l-365260 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

The objective of the present study was to determine the effects of spinal cholecystokinin (CCK) receptor antagonists on morphine antinociception in a model of visceral nociception, colorectal distension, in rats with chronic colonic inflammation and vehicle-treated controls. Three to five days after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS), an enhanced visceromotor response to all pressures of colorectal distension (10-80 mm Hg) was evident. The ED(50) of intrathecal morphine (0.93 microgram) in vehicle-treated rats produced significantly greater antinociception in TNBS-treated rats. Intrathecal proglumide, a nonselective CCK receptor antagonist, dose dependently enhanced the antinociceptive effect of morphine in vehicle-treated rats, but not in TNBS-treated rats. Similarly, L-365, 260, a specific CCK(B) receptor antagonist, dose dependently increased morphine's antinociceptive effects in vehicle-treated rats but had no effect in rats with TNBS-induced colonic inflammation. L-364,718, a specific CCK(A) receptor antagonist, had no effect on morphine antinociception in either vehicle-treated or TNBS-treated rats. These data indicate that CCK, acting at the CCK(B) receptor, is involved in modulating morphine antinociception following a noxious visceral stimulus. However, CCK receptor antagonists no longer enhance morphine antinociception after instillation of intracolonic TNBS, suggesting that visceral inflammation may lead to a reduction in spinal CCK release.

Topics: Analgesics; Anesthesia; Animals; Benzodiazepinones; Colitis; Colon; Devazepide; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Male; Morphine; Phenylurea Compounds; Proglumide; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Rectum; Spinal Cord; Time Factors; Trinitrobenzenesulfonic Acid; Viscera