Show simple item record

dc.contributor.authorLexmond, Willem S.en_US
dc.contributor.authorRufo, Paul A.en_US
dc.contributor.authorFiebiger, Eddaen_US
dc.contributor.authorLencer, Wayne I.en_US
dc.date.accessioned2015-11-03T15:57:52Z
dc.date.issued2015en_US
dc.identifier.citationLexmond, Willem S., Paul A. Rufo, Edda Fiebiger, and Wayne I. Lencer. 2015. “Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy.” PLoS Neglected Tropical Diseases 9 (9): e0004098. doi:10.1371/journal.pntd.0004098. http://dx.doi.org/10.1371/journal.pntd.0004098.en
dc.identifier.issn1935-2727en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23473940
dc.description.abstractBackground and Aims Morbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca2+-gated K+ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na+-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na+-coupled glucose uptake. Materials and Methods Short-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers. Results: Treatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90). Conclusion: Treatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca2+-dependent agonists as expected, but did not affect Na+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pntd.0004098en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583490/pdf/en
dash.licenseLAAen_US
dc.titleElectrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapyen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Neglected Tropical Diseasesen
dash.depositing.authorLexmond, Willem S.en_US
dc.date.available2015-11-03T15:57:52Z
dc.identifier.doi10.1371/journal.pntd.0004098*
dash.contributor.affiliatedRufo, Paul
dash.contributor.affiliatedLencer, Wayne
dash.contributor.affiliatedFiebiger, Edda
dash.contributor.affiliatedLexmond, Willem S.


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record