Anion transport pathways involved in PG E2 and acid-stimulated murine duodenal bicarbonate secretion in vivo

A. Singh; A. Krabbenhöft; B. Riederer; M. Manns; M. Soleimani; U. Seidler

doi:10.1055/s-2006-950645

Zeitschrift für Gastroenterologie, Table of Contents

Anion transport pathways involved in PG E2 and acid-stimulated murine duodenal bicarbonate secretion in vivo

A Singh ¹, A Krabbenhöft ², B Riederer ², M Manns ², M Soleimani ³, U Seidler ²

¹Medizinische Hochschule Hannover, Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
²Medizinische Hochschule Hannover, Hannover, Germany
³University of Cincinnati, Cincinnati, United States of America

Abstract

Aims: Duodenal HCO3- secretion is an important factor in epithelial protection, and mediated by the CFTR anion channel, as well as one or several anion exchangers of the SLC26 family. It is stimulated by contact of the epithelium with acid. This acid-induced stimulation is largely mediated via the release of endogenous prostaglandins. Recently, we found that duodenal mucosa in vitro of mice lacking the anion exchanger PAT1 (Slc26a6) displays a mild reduction in basal, and a severe reduction in PG E2-stimulated HCO3- secretion (Gastroenterology 2006;130:349–58). Aim: To determine whether PAT1 is involved in acid-stimulated duodenal epithelial HCO3- secretion in vivo.

Methods: PAT1 and CFTR +/+ and -/- mice were anesthetized, the proximal duodenum was cannulated and perfused with isotonic saline, and [HCO3-] was determined in the perfusate.

Results: Basal HCO3- secretion was not significantly different in PAT1 -/- vs. wt, (2.09±0.12 vs. 2.36±0.27µmol/cm2h p=0.37), but was dramatically different in CFTR -/- vs. wt mice (0.46±0.08 vs. 3.79±0.25µmol/cm2h, p<0.000001). The HCO3- secretory response elicited by luminal acidification to pH 2 for 5min, was also found to be unaltered in PAT1 -/- vs. wt littermates (net peak, 1.71±0.31 vs. 1.49±0.36µmol/cm2h, respectively (p=0.61). The HCO3- secretory response elicited by 10–5M luminal PG E2, on the other hand, was significantly lower in PAT1 -/- vs. wt mice (net peak, 2.37±0.29 vs. 4.61±0.70µmol/cm2h, respectively (p=0.01), while forskolin-stimulated bicarbonate secretion was not different. CFTR -/- mice displayed a severe reduction in PG E2-stimulated (net peak, 0.48±0.17 vs. 4.22±0.71µmol/cm2h in wt littermates, respectively (p=0.0004), as well as forskolin- and acid-stimulated duodenal bicarbonate secretion.

Conclusions: Consistent with the in vitro data, PG E2-mediated duodenal bicarbonate secretion is reduced in the absence of anion exchanger PAT1 (SLC26A6). However, duodenal HCO3- secretion stimulated by luminal acid is unaltered in the absence of PAT1, but severely reduced in the absence of the CFTR anion channel. The CFTR anion channel is therefore the major pathway that conveys duodenal HCO3- secretion in response to luminal acid.