Functional coupling of apical Cl−/HCO3− exchange with CFTR in stimulated HCO3− secretion by guinea pig interlobular pancreatic duct | Zendy

Andrew K. Stewart | Zendy; Akiko Yamamoto | Zendy; Miyuki Nakakuki | Zendy; Takaharu Kondo | Zendy; Seth L. Alper | Zendy; Hiroki Ishiguro | Zendy

Open Access

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Author(s) -

Andrew K. Stewart,

Akiko Yamamoto,

Miyuki Nakakuki,

Takaharu Kondo,

Seth L. Alper,

Hiroki Ishiguro

Publication year - 2009

Publication title -

ajp gastrointestinal and liver physiology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.644

H-Index - 169

eISSN - 1522-1547

pISSN - 0193-1857

DOI - 10.1152/ajpgi.90697.2008

Subject(s) - dids , chemistry , intracellular ph , apical membrane , hyperpolarization (physics) , pancreatic duct , biophysics , ion transporter , secretion , cotransporter , microbiology and biotechnology , intracellular , pancreas , biochemistry , membrane , biology , sodium , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy

Pancreatic ductal epithelium produces a HCO(3)(-)-rich fluid. HCO(3)(-) transport across ductal apical membranes has been proposed to be mediated by both SLC26-mediated Cl(-)/HCO(3)(-) exchange and CFTR-mediated HCO(3)(-) 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(-)/HCO(3)(-) 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 HCO(3)(-)-CO(2). Intracellular pH recovery upon luminal Cl(-) restoration (nominal Cl(-)/HCO(3)(-) exchange) in cAMP-stimulated ducts was largely inhibited by luminal dihydro-DIDS (H(2)DIDS), 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 HCO(3)(-)-free, Cl(-)-rich solution enhanced cAMP-stimulated HCO(3)(-) secretion, as calculated from changes in luminal pH and volume. Luminal Cl(-) removal produced, after a transient small depolarization, sustained cell hyperpolarization of approximately 15 mV consistent with electrogenic Cl(-)/HCO(3)(-) exchange. The hyperpolarization was inhibited by H(2)DIDS and potentiated by CFTRinh-172. Interlobular ducts expressed mRNAs encoding CFTR, Slc26a6, and Slc26a3, as detected by RT-PCR. Thus Cl(-)-dependent apical HCO(3)(-) secretion in pancreatic duct is mediated predominantly by an Slc26a6-like Cl(-)/HCO(3)(-) exchanger and is accelerated by inhibition of CFTR. This study demonstrates functional coupling between Cftr and Slc26a6-like Cl(-)/HCO(3)(-) exchange activity in apical membrane of guinea pig pancreatic interlobular duct.

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