Chloride-bicarbonate exchangers in the human fetal pancreas

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmem brane conductance regulator (CFTR) gene that encodes a small conductance cA MP-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-/HCO3-) exc hanger, located in the apical membrane of pancreatic duct cells. The molecu lar basis of this Cl-/HCO3- exchanger has not been identified. A combinatio n of screening cDNA libraries, RNase protection, and 5 ' RACE analysis was used to identify Cl-/HCO3- exchangers in human fetal pancreas. An AE2 Cl-/H CO3- exchanger was shown to be expressed in human fetal pancreas from the m idtrimester of gestation, at a time when CF-associated pathology commences. In addition, an AE1 Cl-/HCO3 was identified in fetal pancreas but was abse nt from the adult pancreas and cultured ductal epithelial cells from fetal and adult pancreas. (C) 1999 Academic Press.