Involvement of the anion exchanger SLC26A6 in prostaglandin E2- but not forskolin-stimulated duodenal HCO3- secretion.
OBJECTIVE
SLC26A6 is a recently identified apical Cl(-)/HCO(3)(-) exchanger with strong expression in murine duodenum. The present study was designed to examine the role of SLC26A6 in prostaglandin E(2) (PGE(2))-, forskolin-, and carbachol-induced duodenal HCO(3)(-) secretion.


METHODS
Murine duodenal mucosal HCO(3)(-) secretion was examined in vitro in Ussing chambers and mucosal SLC26A6 expression levels were analyzed by semiquantitative reverse-transcription polymerase chain reaction.


RESULTS
Basal HCO(3)(-) secretion was diminished by 20%, PGE(2)-stimulated HCO(3)(-) secretory response by 59%, and carbachol-stimulated response was reduced by 35% in SLC26A6-/- compared with +/+ duodenal mucosa, whereas the forskolin-stimulated HCO(3)(-) secretory response was not different. In Cl(-)-free solutions, PGE(2)- and carbachol-stimulated HCO(3)(-) secretion was reduced by 81% and 44%, respectively, whereas forskolin-stimulated HCO(3)(-) secretion was not altered significantly. PGE(2) and carbachol, but not forskolin, were able to elicit a Cl(-)-dependent HCO(3)(-) secretory response in the absence of short-circuit current changes in cystic fibrosis transmembrane conductance regulator knockout mice.


CONCLUSIONS
In murine duodenum, PGE(2)-mediated HCO(3)(-) secretion is strongly SLC26A6 dependent and cystic fibrosis transmembrane conductance regulator independent, whereas forskolin-stimulated HCO(3)(-) secretion is completely SLC26A6 independent and cystic fibrosis transmembrane conductance regulator dependent. Carbachol-induced secretion is less pronounced, but occurs via both transport pathways. This suggests that PGE(2) and forskolin activate distinct HCO(3)(-) transport pathways in the murine duodenum.
Department of Gastroenterology and Hepatology, Hannover Medical School, Germany.
Biguang
B
Tuo
Brigitte
B
Riederer
Zhaohui
Z
Wang
William H
WH
Colledge
Manoocher
M
Soleimani
Ursula
U
Seidler
D000818:Animals; D017920:Antiporters / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000076988:Sulfate Transporters
D017920:Antiporters; D001639:Bicarbonates; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D002217:Carbachol; D015232:Dinoprostone