ACID-STIMULATED DUODENAL BICARBONATE SECRETION INVOLVES A CFTR-MEDIATED TRANSPORT PATHWAY IN MICE

Background & Aims: Duodenal bicarbonate secretion is an important fact or in epithelial protection, The role of the cystic fibrosis transmemb rane conductance regulator (CFTR) in acid-induced bicarbonate secretio n is unknown, The aim of this study was to determine whether CFTR medi ates acid-stimulated duodenal epithelial bicarbonate secretion, Method s: Basal and stimulated bicarbonate secretion was examined in the cyst ic fibrosis murine model cftr(m1UNC), which displays defective CFTR in various organs including chloride transport abnormalities in epitheli a. After anesthesia, the proximal duodenum was cannulated and perfused with isotonic saline, and [HCO3-] was determined, Results: Basal bica rbonate secretion was diminished in cystic fibrosis vs, normal mice, 2 .8 +/- 0.7 vs. 4.7 +/- 1.7 mu mol cm(-1).h(-1), respectively (P < 0.00 1). Luminal acidification failed to elicit a bicarbonate secretory res ponse in cystic fibrosis compared with normal littermates (peak respon se, 2.3 +/- 0.2 vs, 9.9 +/- 1.5 mu mol.cm(-1).h(-1), respectively; P < 0.01), Prostaglandin E-2- and vasoactive intestinal peptide-stimulate d bicarbonate secretion were also significantly impaired in cystic fib rosis, Defective bicarbonate secretion in cystic fibrosis genotypes wa s due to decreased net fluid secretion and [HCO3-]. Conclusions: Basal and stimulated proximal duodenal bicarbonate secretion may involve a CFTR-mediated transport pathway, It is likely that CFTR, directly or i ndirectly, has a major functional role in mediating bicarbonate transp ort in the proximal duodenum.