Mechanism of augmented duodenal HCO(3)(-) secretion after elevation of luminal CO(2).

The proximal duodenum is exposed to extreme elevations of P(CO(2)) because of the continuous mixture of secreted HCO(3)(-) with gastric acid. These elevations (up to 80 kPa) are likely to place the mucosal cells under severe acid stress. Furthermore, we hypothesized that, unlike most other cells, the principal source of CO(2) for duodenal epithelial cells is from the lumen.

Cystic fibrosis gene mutation reduces epithelial cell acidification and injury in acid-perfused mouse duodenum.

Background & Aims: Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) is associated with diminished duodenal HCO3- secretion, despite a reported lack of clinical duodenal ulceration in affected subjects. We hypothesized that duodenal epithelial cells expressing a mutant CFTR have enhanced resistance to acid-induced injury. To test this hypothesis, we measured duodenal epithelial cell intracellular pH (pHi), injury, and acid back-diffusion in response to a luminal acid challenge in transgenic mice.

Low-dose PGE2 mimics the duodenal secretory response to luminal acid in mice.

Luminal exposure to concentrated acid, the most accepted physiological stimulus for duodenal bicarbonate secretion (DBS), cannot be used with in vitro preparations due to potential tissue damage. We thus examined whether exposure to PGE(2), a well-characterized physiological duodenal secretagogue, could mimic the effects of acid perfusion. DBS was measured in C57/BL mice by pH-stat/back-titration and measurement of total dissolved CO(2) concentration ([CO(2)](t)).

NHE3 inhibition activates duodenal bicarbonate secretion in the rat.

We examined the effect of inhibition of Na+/H+ exchange (NHE) on duodenal bicarbonate secretion (DBS) in rats to further understand DBS regulation. DBS was measured by using the pH-stat method and by using CO2-sensitive electrodes. 5-(N,N-dimethyl)-amiloride (50 microM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS.

Role of protein kinases on acid-induced duodenal bicarbonate secretion in rats.

We examined the effect of several protein kinase inhibitors, such as staurosporine for protein kinase C (PKC), H-89 for protein kinase A (PKA) and genistein for tyrosine kinase (TK) on acid-induced duodenal bicarbonate secretion (DBS) in rats. HCO(-)(3) secretion was measured using the pH-stat method. Mucosal acidification was performed by perfusing the duodenal loop for 10 min with pH 2.