[-] Show simple item record

dc.contributor.advisorClarke, Lane L. (Lane Leroy)en
dc.contributor.authorSimpson, Janet Elizabeth, 1976-en_US
dc.date.issued2006eng
dc.date.submitted2006 Summeren
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.en_US
dc.descriptionVita.en_US
dc.description"August 2006"en_US
dc.descriptionIncludes bibliographical references.en_US
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2006.en_US
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Veterinary biomedical sciences.en_US
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.en_US
dc.identifier.merlin.b58495691en_US
dc.identifier.oclc124040690en_US
dc.identifier.otherSimpsonJ-072006-D5220en_US
dc.identifier.urihttp://hdl.handle.net/10355/4391
dc.publisherUniversity of Missouri--Columbiaen_US
dc.relation.ispartof2006 Freely available dissertations (MU)en_US
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2006 Dissertations
dc.subject.lcshDuodenum -- Pathophysiologyen_US
dc.subject.lcshCystic fibrosis geneen_US
dc.subject.lcshBicarbonate ionsen_US
dc.subject.lcshMembrane proteinsen_US
dc.titleThe cystic fibrosis transmembrane conductance regulator and acid-base transporters of the murine duodenumen_US
dc.typeThesisen_US
thesis.degree.disciplineVeterinary biomedical sciencesen_US
thesis.degree.disciplineVeterinary biomedical scienceseng
thesis.degree.grantorUniversity of Missouri--Columbiaen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePh. D.en_US


Files in this item

[PDF]
[PDF]
[PDF]

This item appears in the following Collection(s)

[-] Show simple item record