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Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO_(3)~(-) secretion by pancreatic duct cells

Ishiguro H, Steward M, Naruse S

Departments of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya 464-8601；Japan

Abstract

Pancreatic duct cells secrete HCO_(3)~(-) ions into a HCO_(3)~(-)-rich luminal fluid （-140 mmol/L in human） against at least a 6-fold concentration gradient. Candidate mechanisms for HCO_(3)~(-) transport across the apical membrane include Cl~(-)-HCO_(3)~(-) exchange by an SLC26 anion transporter and diffusion via the HCO_(3)~(-) conductance of cystic fibrosis transmembrane conductance regulator （CFTR） Members of the SLC26 family are known to mediate Cl~(-)-HCO_(3)~(-) exchange across the apical membrane of other epithelia and botl SLC26A6 and SLC26A3 have been detected in pancreatic ducts. Co-expression studies have also revealed that murine slc26a6 ant 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~(-)-2HCO_(3)~(-) exchange and slc26a3 mediating 2Cl~(-)-1HCO_(3)~(-) exchange. Recent experiments using isolated pancreatic ducts from slc26a6~(-/-) mice suggest that slc26a6 mediates most of the Cl~(-)-dependent secretion of HCO_(3)~(-) 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 HCO_(3)~(-) secretion is less clear because human ducts are capable of secreting much higher concentrations of HCO_(3)~(-). The role of SLC26A6 must now be evaluated in a species such as the guinea pig which, like the human, is capable of secreting HCO_(3)~(-) at a concentration of -140 mmol/L. From existing guinea pig data we calculate that a 1Cl~(-)-2HCO_(3)~(-) exchanger such as slc26a6 would be unable to secrete HCO_(3)~(-) against such a steep gradient. On the other hand, the HCO_(3)~(-) conductance of CFTR could theoretically support secretion of HCO_(3)~(-) to a much higher concentrations. CFTR may therefore play a more important role than SLC26A6 in HCO_(3)~(-) secretion by the guinea pig and human pancreas.

Key words: cystic fibrosis transmembrane conductance regulator;SLC26;pancreatic duct;bicarbonate secretion

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Citing This Article：

Ishiguro H, Steward M, Naruse S. Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO_(3)~(-) secretion by pancreatic duct cells. Acta Physiol Sin 2007; 59 (4): 465-476 (in Chinese with English abstract).