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dc.contributor.authorMansley, Morag K.
dc.contributor.authorNiklas, Christian
dc.contributor.authorNacken, Regina
dc.contributor.authorMandery, Kathrin
dc.contributor.authorGlaeser, Hartmut
dc.contributor.authorFromm, Martin F.
dc.contributor.authorKorbmacher, Christoph
dc.contributor.authorBertog, Marko
dc.date.accessioned2020-07-09T15:30:01Z
dc.date.available2020-07-09T15:30:01Z
dc.date.issued2020-05-22
dc.identifier.citationMansley , M K , Niklas , C , Nacken , R , Mandery , K , Glaeser , H , Fromm , M F , Korbmacher , C & Bertog , M 2020 , ' Prostaglandin E 2 stimulates the epithelial sodium channel (ENaC) in cultured mouse cortical collecting duct cells in an autocrine manner ' , Journal of General Physiology , vol. 152 , no. 8 , e201912525 . https://doi.org/10.1085/jgp.201912525en
dc.identifier.issn0022-1295
dc.identifier.otherPURE: 268897254
dc.identifier.otherPURE UUID: f0b90d1a-e116-45bd-ba4d-4eb5495b0988
dc.identifier.otherScopus: 85085538055
dc.identifier.otherPubMed: 32442241
dc.identifier.urihttp://hdl.handle.net/10023/20227
dc.descriptionFunding: This study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 387509280, SFB 1350), the Alexander von Humboldt Foundation (3.3-GRO/1143730 STP), the Interdisziplin ̈ares Zentrum für KlinischeForschung of Friedrich-Alexander University (IZKF, TP-A33), and the Bayerische Forschungsstiftung (PDOK-74-10).en
dc.description.abstractProstaglandin E2 (PGE2) is the most abundant prostanoid in the kidney, affecting a wide range of renal functions. Conflicting data have been reported regarding the effects of PGE2 on tubular water and ion transport. The amiloride-sensitive epithelial sodium channel (ENaC) is rate limiting for transepithelial sodium transport in the aldosterone-sensitive distal nephron. The aim of the present study was to explore a potential role of PGE2 in regulating ENaC in cortical collecting duct (CCD) cells. Short-circuit current (ISC) measurements were performed using the murine mCCDcl1 cell line known to express characteristic properties of CCD principal cells and to be responsive to physiological concentrations of aldosterone and vasopressin. PGE2 stimulated amiloride-sensitive ISC via basolateral prostaglandin E receptors type 4 (EP4) with an EC50 of ∼7.1 nM. The rapid stimulatory effect of PGE2 on ISC resembled that of vasopressin. A maximum response was reached within minutes, coinciding with an increased abundance of β-ENaC at the apical plasma membrane and elevated cytosolic cAMP levels. The effects of PGE2 and vasopressin were nonadditive, indicating similar signaling cascades. Exposing mCCDcl1 cells to aldosterone caused a much slower (∼2 h) increase of the amiloride-sensitive ISC. Interestingly, the rapid effect of PGE2 was preserved even after aldosterone stimulation. Furthermore, application of arachidonic acid also increased the amiloride-sensitive ISC involving basolateral EP4 receptors. Exposure to arachidonic acid resulted in elevated PGE2 in the basolateral medium in a cyclooxygenase 1 (COX-1)-dependent manner. These data suggest that in the cortical collecting duct, locally produced and secreted PGE2 can stimulate ENaC-mediated transepithelial sodium transport.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofJournal of General Physiologyen
dc.rightsCopyright © 2020 Mansley et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).en
dc.subjectQH301 Biologyen
dc.subjectQP Physiologyen
dc.subjectPhysiologyen
dc.subject3rd-NDASen
dc.subject.lccQH301en
dc.subject.lccQPen
dc.titleProstaglandin E2 stimulates the epithelial sodium channel (ENaC) in cultured mouse cortical collecting duct cells in an autocrine manneren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1085/jgp.201912525
dc.description.statusPeer revieweden
dc.identifier.urlhttps://rupress.org/jgp/article/152/8/e201912525/151804/Prostaglandin-E2-stimulates-the-epithelial-sodiumen


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