Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a small conductance cAMP-activated chloride ion channel. In the CF pancreatic duct, mutations in CFTR cause a reduction in bicarbonate secretion. This is thought to result from CFTR operating in parallel with a chloride-bicarbonate (Cl(-)/HCO(-)(3)) exchanger, located in the apical membrane of pancreatic duct cells. The molecular basis of this Cl(-)/HCO(-)(3) exchanger has not been identified. A combination of screening cDNA libraries, RNase protection, and 5' RACE analysis was used to identify Cl(-)/HCO(-)(3) exchangers in human fetal pancreas. An AE2 Cl(-)/HCO(-)(3) exchanger was shown to be expressed in human fetal pancreas from the midtrimester of gestation, at a time when CF-associated pathology commences. In addition, an AE1 Cl(-)/HCO(3) was identified in fetal pancreas but was absent from the adult pancreas and cultured ductal epithelial cells from fetal and adult pancreas.

Original publication

DOI

10.1006/bbrc.1999.1367

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

24/09/1999

Volume

263

Pages

315 - 321

Keywords

Adult, Anion Exchange Protein 1, Erythrocyte, Anion Transport Proteins, Antiporters, Base Sequence, Bicarbonates, Chloride-Bicarbonate Antiporters, Chlorides, Cystic Fibrosis Transmembrane Conductance Regulator, DNA, Complementary, Fetus, Gene Library, Humans, Membrane Proteins, Molecular Sequence Data, Pancreatic Ducts, SLC4A Proteins