Show simple item record

dc.contributor.authorPelish, Henry Efrem
dc.contributor.authorCiesla, William
dc.contributor.authorTanaka, Nori
dc.contributor.authorReddy, Krishna Podditur
dc.contributor.authorShair, Matthew David
dc.contributor.authorKirchhausen, Tomas Leopold
dc.contributor.authorLencer, Wayne Isaac
dc.date.accessioned2017-07-18T19:38:31Z
dc.date.issued2006
dc.identifierQuick submit: 2017-05-11T14:38:25-0400
dc.identifier.citationPelish, Henry E., William Ciesla, Nori Tanaka, Krishna Reddy, Matthew D. Shair, Tomas Kirchhausen, and Wayne I. Lencer. 2006. “The Cdc42 Inhibitor Secramine B Prevents cAMP-Induced K+ Conductance in Intestinal Epithelial Cells.” Biochemical Pharmacology 71 (12) (June): 1720–1726. doi:10.1016/j.bcp.2006.03.011.en_US
dc.identifier.issn0006-2952en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33464219
dc.description.abstractCyclic AMP- (cAMP) and calcium-dependent agonists stimulate chloride secretion through the coordinated activation of distinct apical and basolateral membrane channels and ion transporters in mucosal epithelial cells. Defects in the regulation of Cl– transport across mucosal surfaces occur with cystic fibrosis and V. cholerae infection and can be life threatening. Here we report that secramine B, a small molecule that inhibits activation of the Rho GTPase Cdc42, reduced cAMP-stimulated chloride secretion in the human intestinal cell line T84. Secramine B interfered with a cAMP-gated and Ba2+-sensitive K+ channel, presumably KCNQ1/KCNE3. This channel is required to maintain the membrane potential that sustains chloride secretion. In contrast, secramine B did not affect the Ca2+-mediated chloride secretion pathway, which requires a separate K+ channel activity from that of cAMP. Pirl1, another small molecule structurally unrelated to secramine B that also inhibits Cdc42 activation in vitro, similarly inhibited cAMP-dependent but not Ca2+-dependent chloride secretion. These results suggest that Rho GTPases may be involved in the regulation of the chloride secretory response and identify secramine B an inhibitor of cAMP-dependent K+ conductance in intestinal epithelial cells.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.bcp.2006.03.011en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511784/en_US
dash.licenseLAA
dc.subjectSecramineen_US
dc.subjectChloride secretionen_US
dc.subjectCdc42en_US
dc.subjectcAMPen_US
dc.subjectPotassium channel regulationen_US
dc.subjectKCNQ1/KCNE3en_US
dc.titleThe Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cellsen_US
dc.typeJournal Articleen_US
dc.date.updated2017-05-11T18:37:53Z
dc.description.versionAccepted Manuscripten_US
dc.relation.journalBiochemical Pharmacologyen_US
dash.depositing.authorShair, Matthew David
dc.date.available2006
dc.date.available2017-07-18T19:38:31Z
dc.identifier.doi10.1016/j.bcp.2006.03.011*
dash.contributor.affiliatedPelish, Henry E.
dash.contributor.affiliatedLencer, Wayne
dash.contributor.affiliatedReddy, Krishna
dash.contributor.affiliatedKirchhausen, Tomas
dash.contributor.affiliatedShair, Matthew


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record