When gastric acid mixes with duodenal HCO3¯ high levels of CO2 are generated. The CO2 enters the enterocytes by diffusion, and HCO3¯ is formed intracellularly in a reaction catalyzed by carbonic anhydrase (CA). The duodenal bicarbonate secretion (DBS), and in particular the ability of the mucosa to respond to luminal acid with a rise in secretion, are deficient in patients with duodenal ulcer disease. The duodenal secretory response to luminal acid involves mediation by prostaglandin E2 (PGE2) and PGE2 is a duodenal secretagogue in all species.

CA II- and IX-deficient mice and different combinations of their heterozygous and WT counterparts were studied. The mice were anesthetized by isoflurane. A segment of the proximal duodenum was isolated and DBS was titrated. Arterial blood pressure was recorded and blood acid/base balance was analyzed.

The duodenal segment secreted HCO3¯ at a steady basal rate of 5.3 ± 0.6 mmol?cm¯1?h¯1. Perfusing the duodenal lumen for 20 min with 47 mM PGE2 caused a significant increase in DBS to 13.0 ± 2.9 mmol?cm¯1?h¯1. The DBS response to PGE2 was completely absent in Car2-/- mice, whereas basal DBS was normal. The CA IX-deficient mice with normal Car2 alleles showed a slight increase in basal as well as stimulated DBS. Histological abnormalities were observed in the gastroduodenal epithelium in both CA II- and IX-deficient mice.

The results show clearly that CA II activity plays an essential role in the PGE2-stimulated DBS. Thus, none of the CA II-deficient mice did increase alkaline secretion when stimulated with PGE2.