Concentration-dependent effects of disulfonic stilbenes on colonic chloride transport

P. L. Smith, S. K. Sullivan, R. D. McCabe

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Abstract

Stripped rabbit colonic mucosa was studied in vitro in Ussing chambers to determine effects of the disulfonic stilbenes 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and the diuretic furosemide on unidirectional and net Cl fluxes. Results from these studies reveal that SITS (1 mM) added to either the serosal or mucosal bathing solution reduced both unidirectional Cl fluxes with no significant change in net Cl flux. The effects of SITS do not appear to be mediated by an effect on the shunt permeability since SITS (1 mM) did not alter either the intercept or slope of the Na concentration dependence of the serosal-to-mucosal Na flux. Furosemide (1 mM) decreased the serosal-to-mucosal Cl flux without altering short-circuit current (I(sc)) when added to the luminal bathing solution and reduced both unidirectional fluxes and increased I(sc) when added to the serosal bathing solution. DIDS (0.5 mM) added to the luminal bathing solution did not alter unidirectional Cl fluxes or I(sc). However, serosal addition of DIDS produced dose-dependent changes in Cl transport. At 5 μM DIDS reduced the mucosal-to-serosal Cl flux without altering the serosal-to-mucosal flux or I(sc). At 50 μM DIDS reduced the mucosal-to-serosal Cl flux and increased I(sc), and at 0.5 mM DIDS increased the serosal-to-mucosal Cl flux, reduced the mucosal-to-serosal Cl flux, and increased I(sc) and transepithelial conductance. The effect of 0.5 mM DIDS on I(sc) was reduced by Ca removal from the serosal bathing solution and by the loop diuretics furosemide and bumetanide. The effects of 0.5 mM but not 5 μM DIDS on Cl fluxes and I(sc) were reduced by the prostaglandin synthesis inhibitors indomethacin (10 μM) and flufenamic acid (10 μM). These results indicate the disulfonic stilbenes produce dose-dependent changes in colonic ion transport that cannot be ascribed simply to inhibition of anion exchange. Furthermore, the increase in electrogenic Cl secretion produced by disulfonic stilbenes appears to occur by a Ca-mediated increase in prostaglandin synthesis.

Original languageEnglish
Pages (from-to)G44-G49
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume250
Issue number1 (13/1)
DOIs
StatePublished - 1986

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