| Autor: |
Stewart, A. K., Yamamoto, A., Nakakuki, M., Kondo, T., Alper, S. L., Ishiguro, H. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Jun2009, Vol. 296, pG1307-G1317, 11p |
| Abstrakt: |
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 CETR, 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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