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Key role of CFTR for all modes of intestinal HCO 3 − secretion
Author(s) -
Singh Anurag Kumar,
Zheng Wen,
Sjöblom Markus,
Seidler Ursula
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.998.18
Subject(s) - secretion , chemistry , carbachol , bicarbonate , sodium–hydrogen antiporter , apical membrane , intestinal mucosa , forskolin , medicine , biochemistry , in vitro , receptor , membrane , sodium , organic chemistry
Background CF patients suffer from a variety of gastrointestinal problems, which may all be directly or indirectly linked to the inability of the intestinal mucosa to secrete HCO 3 − and to inhibit Na + /H + mediated fluid absorption and proton secretion. Aim To delineate the dependency of different modes of intestinal HCO 3 − secretion on CFTR expression. Methods and Results We studied acid‐, agonist‐, and HCO 3 − stimulated, as well as Cl − ‐dependent HCO 3 − secretion in the CFTR tm1cam and WT murine duodenum in vivo . NHE3 and Slc26a6‐deficient mice were used for selected questions. In WT mice, luminal acid, forskolin, heat‐stable E. coli enterotoxin (STa), PG E 2 , carbachol, and an increase of blood HCO 3 − all stimulated duodenal HCO 3 − secretion in anesthetized WT but not in CFTR tm1cam mice. Pharmacological inhibition or genetic ablation of NHE3 resulted in a significantly higher basal HCO 3 − secretory rate, which was electroneutral and therefore due to an unmasking of apical Cl − /HCO 3 − exchange activity. Accordingly, Slc26a6 as well as Slc26a3 ablation attenuated S1611‐induced J HCO3‐ . In the absence of CFTR, electroneutral NaCl absorptive rates were similar to wt rates, but S1611 induced virtually no increase in HCO 3 − secretion. Conclusion This indicates that the apical anion exchangers Slc26a6 and Slc26a3 need proton recycling via NHE3 to operate in the Cl − absorptive mode, and Cl − exit via CFTR to operate in the HCO 3 − secretory mode.