Background and Aims: 

The HCO3 ^- secretion by the duodenal epithelium (DBS) is under central nervous as well as local mucosal neurohumoral control, and is a primary mechanism in mucosal protection against acid from the stomach. Carbonic anhydrase (CA) is strongly expressed in the duodenum and has been implicated in a variety of physiological functions including enterocyte HCO3 ^- supply for secretion and the "sensing" of luminal acid and CO2. The aim of the present study was to elucidate the role of intracellular CA II in acid-induced murine DBS in vivo.

Methods: 

A ~10-mm segment of the proximal duodenum with intact blood supply was perfused under different experimental conditions and DBS was titrated by pH-stat. Two-photon confocal microscopy using the pH-sensitive dye SNARF-1F were used to assess duodenocyte pHi in vivo.

Results: 

The duodenal bicarbonate secretory response to acid was abolished in CA II-deficient mice, but normal to forskolin-or 16,16-dimethyl prostaglandin E2 stimulation. Complete inhibition of CAs by luminal methazolamide and intravenous acetazolamide completely inhibited the response to acid, but did not alter the response to forskolin. While duodenocytes acidified upon luminal perfusion with acid, no significant pHi change occurred in CA II-deficient duodenum.

Conclusion: 

The results suggest that CA II is important for duodenocyte acidification by low luminal pH and for eliciting the acid-mediated HCO3 ^- secretory response, but is not important in the generation of the secreted HCO3 ^- ions.