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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark
DIFFERENTIAL INVOLVEMENT OF SLC26A3 (DRA), CFTR, AND OTHER HCO3- TRANSPORTERS IN MURINE ILEAL, PROXIMAL AND DISTAL COLONIC HCO3- SECRETION
Abstract number: P-MON-92
Xiao1 F, Singh1 A, Chen1 M, Li1 J, Riederer1 B, Bonhagen1 J, Juric1 M, Bachmann1 O, Soleimani1 M, Seidler1 U
Backround: Intestinal HCO3- secretion is necessary for mucin and paneth cell secretion, mu-cosal protection and repair. We therefore had previously studied chronic inflammation- associated changes in intestinal HCO3- secretion in a TNF-a overexpressing mouse model, and had observed dramatic, but segment specific changes in HCO3- secretion. Aim and methods: To understand these complex inflammation-associated disturbances, we studied the basal and FSK- stimulated HCO3- secretion in isolated distal ileal, proximal and distal colonic mucosa of mice deficient for the Cl-/HCO3- exchanger Slc26a3 and the anion channel CFTR before and after luminal Cl- substitution. The obtained results were then compared with those obtained in the inflamed mucosa of TNFDare +/ and noninflamed WT. Results: Ileal and dis-tal colonic mucosa displayed high basal HCO3- secretory rates, which were dramatically de- creased in the absence of Slc26a3 or removal of luminal Cl-. Stimulation by FSK induced an identical increase in HCO3- secretion both in Slc26a3-deficient and WT mucosa, which was completely CFTR-dependent in the ileum but not the colon. In the proximal colon, basal HCO3- secretion was markedly lower than in the ileum or distal colon, neither reduced in Slc26a3 nor in CFTR-deficient mucosa, but briskly stimulated by FSK in a CFTR-independent fashion. Conclusions: In murine distal ileum and distal colon, the high basal HCO3- secretory rates are largely Cl- dependent and Slc26a3-mediated, whereas they are low, Cl- -independent and not Slc26a3-mediated in the proximal colon. FSK elicits a CFTR-dependent HCO3- secretory response in the ileum and a CFTR-independent one in the colon. Chronic inflammation abolishes the Cl--dependent, Slc26a3-mediated HCO3- secretion and interferes with FSK-stimulated, CFTR- dependent HCO3- secretion, but stimulates the colonic CFTR-independent HCO3- secretion. These data help explain inflammation-associated distur- bances in intestinal barrier function.
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Acta Physiologica 2010; Volume 198, Supplement 677 :P-MON-92