Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct.
The role of Slc26a6 (PAT1) on apical Cl-/HCO3- exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice. Apical Cl-/HCO3- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO3(-)-influx mode of apical [Cl-]i/[HCO3-]o exchange (where brackets denote concentration and subscripts i and o denote intra- and extracellular, respectively) was dramatically upregulated in Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO3(-)-efflux mode of apical [Cl-]o/[HCO3-]i exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT), suggesting the unidirectionality of the Slc26a6-mediated HCO3- transport. Fluid secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice (P > 0.05). In addition, when pancreatic juice was collected from whole animal in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semiquantitative RT-PCR demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in Slc26a6 knockout pancreas. In conclusion, these results point to the role of Slc26a6 in HCO3- efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.
Ishiguro
Hiroshi
H
Laboratory of Human Nutrition, Nagoya Univ. Graduate School of Medicine, Nagoya, Japan. ishiguro@htc.nagoya-u.ac.jp
Namkung
Wan
W
Yamamoto
Akiko
A
Wang
Zhaohui
Z
Worrell
Roger T
RT
Xu
Jie
J
Lee
Min Goo
MG
Soleimani
Manoocher
M
D000818:Animals; D017920:Antiporters / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010183:Pancreatic Ducts / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012633:Secretin / Q000494:pharmacology; D000076988:Sulfate Transporters
D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; C489860:Slc26a3 protein, mouse; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D012633:Secretin; D000242:Cyclic AMP