The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum

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The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/4391

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dc.contributor.advisor Clarke, Lane L. (Lane Leroy) en
dc.contributor.author Simpson, Janet Elizabeth, 1976- en_US
dc.date.accessioned 2010-01-12T17:06:19Z
dc.date.available 2010-01-12T17:06:19Z
dc.date.issued 2006 en_US
dc.date.submitted 2006 Summer en
dc.identifier.other SimpsonJ-072006-D5220 en_US
dc.identifier.uri http://hdl.handle.net/10355/4391
dc.description The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. en_US
dc.description Vita. en_US
dc.description "August 2006" en_US
dc.description Includes bibliographical references. en_US
dc.description Thesis (Ph. D.) University of Missouri-Columbia 2006. en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- Veterinary biomedical sciences. en_US
dc.description.abstract The alkaline mucus barrier of the duodenum plays an important role in protecting the epithelium from acidic chyme entering from the stomach. Active HCO₃⁻ secretion involves the apical membrane activities of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, the protein that is defective in cystic fibrosis (CF), and Cl⁻/HCO₃⁻ exchangers. Under basal conditions, studies of CF patients and mouse models indicate that HCO₃⁻ secretion by anion exchange predominates. In addition, basal HCO₃⁻ secretion is reduced in the CF duodenum, but the specific pathophysiology for this deficiency has yet to be elucidated. Our studies reveal that Cl⁻ channel activity by CFTR facilitates apical membrane Cl⁻in/HCO₃⁻out exchange by providing a Cl⁻ 'leak' and is responsible for the reduced rate of Cl⁻/HCO₃⁻ exchange in the murine CF intestine. Using mice with gene-targeted deletions of the apical membrane Cl⁻/HCO₃⁻ exchangers PAT-1, DRA, and AE4, PAT-1 was found to be the major Cl⁻/HCO₃⁻ exchanger of the upper villus of the duodenum. Interestingly, these studies also revealed a novel role for PAT-1 as a base-importer (i.e., Cl⁻out/HCO₃⁻in) whereby it interacts with carbonic anhydrase II (CAII), the most widely expressed isozyme of the small intestine, during H⁺/peptide transport to minimize intracellular acidification and sustain nutrient absorption. en_US
dc.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.relation.ispartof 2006 Freely available dissertations (MU) en_US
dc.subject.lcsh Duodenum -- Pathophysiology en_US
dc.subject.lcsh Cystic fibrosis gene en_US
dc.subject.lcsh Bicarbonate ions en_US
dc.subject.lcsh Membrane proteins en_US
dc.title The cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenum en_US
dc.type Thesis en_US
thesis.degree.discipline Veterinary biomedical sciences en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name Ph. D. en_US
thesis.degree.level Doctoral en_US
dc.identifier.merlin .b58495691 en_US
dc.identifier.oclc 124040690 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2006 Dissertations


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