Functional coupling of apical Cl−/HCO3− exchange with CFTR in stimulated HCO3− secretion by guinea pig interlobular pancreatic duct
AUTOR(ES)
Stewart, A. K.
FONTE
American Physiological Society
RESUMO
Pancreatic ductal epithelium produces a HCO3−-rich fluid. HCO3− transport across ductal apical membranes has been proposed to be mediated by both SLC26-mediated Cl−/HCO3− exchange and CFTR-mediated HCO3− conductance, with proportional contributions determined in part by axial changes in gene expression and luminal anion composition. In this study we investigated the characteristics of apical Cl−/HCO3− exchange and its functional interaction with Cftr activity in isolated interlobular ducts of guinea pig pancreas. BCECF-loaded epithelial cells of luminally microperfused ducts were alkalinized by acetate prepulse or by luminal Cl− removal in the presence of HCO3−-CO2. Intracellular pH recovery upon luminal Cl− restoration (nominal Cl−/HCO3− exchange) in cAMP-stimulated ducts was largely inhibited by luminal dihydro-DIDS (H2DIDS), accelerated by luminal CFTR inhibitor inh-172 (CFTRinh-172), and was insensitive to elevated bath K+ concentration. Luminal introduction of CFTRinh-172 into sealed duct lumens containing BCECF-dextran in HCO3−-free, Cl−-rich solution enhanced cAMP-stimulated HCO3− secretion, as calculated from changes in luminal pH and volume. Luminal Cl− removal produced, after a transient small depolarization, sustained cell hyperpolarization of ∼15 mV consistent with electrogenic Cl−/HCO3− exchange. The hyperpolarization was inhibited by H2DIDS and potentiated by CFTRinh-172. Interlobular ducts expressed mRNAs encoding CFTR, Slc26a6, and Slc26a3, as detected by RT-PCR. Thus Cl−-dependent apical HCO3− secretion in pancreatic duct is mediated predominantly by an Slc26a6-like Cl−/HCO3− exchanger and is accelerated by inhibition of CFTR. This study demonstrates functional coupling between Cftr and Slc26a6-like Cl−/HCO3− exchange activity in apical membrane of guinea pig pancreatic interlobular duct.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2697944Documentos Relacionados
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