Chloride-bicarbonate exchangers in the human fetal pancreas.
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.
Hyde
K
K
Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom.
Harrison
D
D
Hollingsworth
M A
MA
Harris
A
A
D000328:Adult; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000378:metabolism; D027321:Anion Transport Proteins; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001639:Bicarbonates / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005333:Fetus / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010183:Pancreatic Ducts / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D064606:SLC4A Proteins
D001457:Anion Exchange Protein 1, Erythrocyte; D027321:Anion Transport Proteins; D017920:Antiporters; D001639:Bicarbonates; C505032:CFTR protein, human; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D018076:DNA, Complementary; D008565:Membrane Proteins; D064606:SLC4A Proteins; C489237:SLC4A3 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator