CFTR drives Na+-nHCO-3 cotransport in pancreatic duct cells: a basis for defective HCO-3 secretion in CF |
| |
Authors: | Shumaker Holli; Amlal Hassane; Frizzell Raymond; Ulrich Charles D II; Soleimani Manoocher |
| |
Abstract: | Pancreatic dysfunction in patients with cystic fibrosis (CF) isfelt to result primarily from impairment of ductalHCO 3 secretion. We provide molecularevidence for the expression of NBC-1, an electrogenicNa+-HCO 3cotransporter (NBC) in cultured human pancreatic ductcells exhibiting physiological features prototypical of CF ductfragments (CFPAC-1 cells) or normal duct fragments CAPAN-1 cellsand CFPAC-1 cells transfected with wild-type CF transmembraneconductance regulator (CFTR)]. We further demonstrate that1)HCO 3 uptake across the basolateralmembranes of pancreatic duct cells is mediated via NBC and2) cAMP potentiates NBC activitythrough activation of CFTR-mediatedCl secretion. We proposethat the defect in agonist-stimulated ductal HCO 3 secretion in patients with CF ispredominantly due to decreased NBC-drivenHCO 3 entry at the basolateralmembrane, secondary to the lack of sufficient electrogenic drivingforce in the absence of functional CFTR. |
| |
Keywords: | |
|
| 点击此处可从《American journal of physiology》浏览原始摘要信息 |
| 点击此处可从《American journal of physiology》下载免费的PDF全文 |