Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E(2)

Duodenal bicarbonate secretion (DBS) is accepted as the primary mucosal defense against acid discharged from the stomach and is impaired in patients with duodenal ulcer disease. The secretory response to luminal acid is the main physiological stimulus for DBS and involves mediation by PGE(2) produced by mucosal cells. The aim of this investigation is to elucidate the role of carbonic anhydrases (CAs) II and IX in PGE(2)-mediated bicarbonate secretion in the murine duodenum. CA II- and IX-deficient mice and different combinations of their heterozygous and WT counterparts were studied. A 10-mm segment of the proximal duodenum with intact blood supply was isolated, and DBS was titrated by pH-stat (TitroLine-easy, Schott, Mainz, Germany). Mean arterial blood pressure (MAP) was continuously recorded, and blood acid/base balance and gastrointestinal morphology were analyzed. The duodenal segment spontaneously secreted HCO(3)(-) at a steady basal rate of 5.3 ± 0.6 μmol·cm(-1)·h(-1). Perfusing the duodenal lumen for 20 min with 47 μM PGE(2) caused a significant increase in DBS to 13.0 ± 2.9 μmol·cm(-1)·h(-1), P < 0.0001. The DBS response to PGE(2) 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 DBS. Histological abnormalities were observed in the gastroduodenal epithelium in both CA II- and IX-deficient mice. Our data demonstrate a gastrointestinal phenotypic abnormality associated with CA II deficiency. The results show that the stimulatory effect of the duodenal secretagogue PGE(2) completely depends on CA II