Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO₃⁻ secretion by pancreatic duct cells.
- Author:
Hiroshi ISHIGURO
1
;
Martin STEWARD
;
Satoru NARUSE
Author Information
1. Departments of Human Nutrition and Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya 464-8601, Japan. ishiguro@htc.nagoya-u.ac.jp
- Publication Type:Journal Article
- MeSH:
Animals;
Bicarbonates;
metabolism;
Chloride-Bicarbonate Antiporters;
physiology;
Cystic Fibrosis Transmembrane Conductance Regulator;
physiology;
Guinea Pigs;
Humans;
Membrane Transport Proteins;
physiology;
Mice;
Pancreatic Ducts;
cytology;
secretion
- From:
Acta Physiologica Sinica
2007;59(4):465-476
- CountryChina
- Language:English
-
Abstract:
Pancreatic duct cells secrete HCO3(-) ions into a HCO3(-)-rich luminal fluid (~140 mmol/L in human) against at least a 6-fold concentration gradient. Candidate mechanisms for HCO3(-) transport across the apical membrane include Cl(-)-HCO3(-)exchange by an SLC26 anion transporter and diffusion via the HCO3(-) conductance of cystic fibrosis transmembrane conductance regulator (CFTR). Members of the SLC26 family are known to mediate Cl(-)-HCO3(-) exchange across the apical membrane of other epithelia and both SLC26A6 and SLC26A3 have been detected in pancreatic ducts. Co-expression studies have also revealed that murine slc26a6 and slc26a3 physically interact with CFTR through the STAS domain of slc26 and the R domain of CFTR, resulting in mutually enhanced activity. Other studies have indicated that these exchangers are electrogenic: slc26a6 mediating 1Cl(-)-2HCO3(-) exchange and slc26a3 mediating 2Cl(-)-1HCO3(-) exchange. Recent experiments using isolated pancreatic ducts from slc26a6(-)/(-) mice suggest that slc26a6 mediates most of the Cl(-)-dependent secretion of HCO3(-) across the apical membrane in the mouse and the data are consistent with the reported electrogenicity of slc26a6. However, the role of SLC26A6 in human pancreatic HCO3(-) secretion is less clear because human ducts are capable of secreting much higher concentrations of HCO3(-). The role of SLC26A6 must now be evaluated in a species such as the guinea pig which, like the human, is capable of secreting HCO3(-) at a concentration of ~140 mmol/L. From existing guinea pig data we calculate that a 1Cl(-)-2HCO3(-) exchanger such as slc26a6 would be unable to secrete HCO3(-) against such a steep gradient. On the other hand, the HCO3(-) conductance of CFTR could theoretically support secretion of HCO3(-) to a much higher concentrations. CFTR may therefore play a more important role than SLC26A6 in HCO3(-) secretion by the guinea pig and human pancreas.
