[-] Show simple item record

dc.contributor.advisorClarke, Lane L. (Lane Leroy)eng
dc.contributor.authorSimpson, Janet Elizabeth, 1976-eng
dc.date.issued2006eng
dc.date.submitted2006 Summereng
dc.descriptionThe 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.eng
dc.descriptionVita.eng
dc.description"August 2006"eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2006.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Veterinary biomedical sciences.eng
dc.description.abstractThe 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.eng
dc.identifier.merlin.b58495691eng
dc.identifier.oclc124040690eng
dc.identifier.otherSimpsonJ-072006-D5220eng
dc.identifier.urihttp://hdl.handle.net/10355/4391eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.subject.lcshDuodenum -- Pathophysiologyeng
dc.subject.lcshCystic fibrosis geneeng
dc.subject.lcshBicarbonate ionseng
dc.subject.lcshMembrane proteinseng
dc.titleThe cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenumeng
dc.typeThesiseng
thesis.degree.disciplineVeterinary biomedical sciences (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


Files in this item

[PDF]
[PDF]
[PDF]

This item appears in the following Collection(s)

[-] Show simple item record