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Effects of chloride conductance inhibitors on fluid secretion into ligated ileal and jejunal loops in pigs
1990
Forsyth, G.W. | Gabriel, S.E.
Compounds that prevent chloride transport in membrane vesicles have been tested for in vivo activity against the effects of intestinal secretory agents. Chloride channel blockers including diphenylamine-2-carboxylate, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate, 5-nitro-2-(2-phenylethylamino)benzoic acid, and alpha-phenylcinnamic acid were tested for effects on jejunal or ileal secretion in weanling pigs. Secretion was studied in ligated intestinal loops in a control state, during exposure to secretory concentrations of theophylline, and after prior treatment with cholera toxin. Increases in net fluid flux induced by either theophylline or cholera toxin were not prevented by adding chloride channel blockers into the intestinal lumen. Channel blocker concentrations that reduced chloride transport by > 50% in pig jejunal brush border vesicles did not cause significant changes in unidirectional blood to lumen chloride flux measured in situ. Several routes of administration of the specific chloride channel blocker alpha-phenylcinnamate failed to reduce fluid secretion induced by theophylline. Chloride channel blocker effectiveness appears to be significantly different between in vitro and in vivo experimental models. In contrast to the chloride channel blockers, loperamide significantly reduced net fluid and chloride flux in ileal loops secreting fluid in response to theophylline. Antagonism of the production or actions of second messenger by loperamide was more effective than the chloride channel blockers in reducing conductive chloride transport associated with intestinal secretion.
Mostrar más [+] Menos [-]Endogenous prostanoids control ion transport across neonatal porcine ileum in vitro
1990
Argenzio, R.A. | Liacos, J.A.
In contrast to the net absorption of Na and Cl ions observed in vivo, porcine small intestine had a net secretion of these ions in vitro. These discrepancies between in vivo and in vitro results have led to difficulties in interpretation of studies investigating mechanisms of intestinal secretion and diarrhea in this species. To examine the influence of endogenous prostanoids on ion transport in neonatal porcine ileum in vitro, tissues were prepared and studied in indomethacin. Net absorption of Na, reversal of net Cl secretion to net absorption, and decreased short circuit current were observed. Conversely, addition of prostaglandins to indomethacin-treated tissues reversed these effects and reestablished conditions similar to those observed in control tissues. Control tissue was essentially refractory to the effects of exogenous prostaglandins. Results indicate that under in vitro conditions, ion transport in neonatal porcine ileum is tightly regulated by endogenous prostanoids that abolish the neutral NaCl absorptive mechanism and elicit electrogenic Cl secretion. However, concentrations of these prostanoids may have been artificially high as a result of tissue preparation for in vitro study.
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