Acetazolamide inhibits basal and stimulated HCO 3− secretion in the human proximal duodenum

Abstract

Background/Aims : Carbonic anhydrase activity plays a role in electrolyte transport in many tissues. This study examined the effect of the carbonic anhydrase inhibitor acetazolamide on human basal and prostaglandin E 2- and acid-stimulated duodenal mucosal bicarbonate secretion and transmucosal electrical potential difference. Methods : Seven healthy volunteers participated in four separate experiments. The variables included oral acetazolamide vs. control test and, as agonists of bicarbonate secretion, either luminal acidification or luminal prostaglandin E 2. The proximal 4 cm of the duodenum (i.e., the duodenal bulb) was isolated between balloons as previously described and perfused with an HCO 3 −-containing (24 mmol/L) balanced electrolyte glucose-containing (10 mmol/L) solution. Results : Acetazolamide treatment significantly decreased mean basal HCO 3 − secretion and basal transmucosal potential difference. After luminal acidification, duodenal mucosal bicarbonate increased significantly after both acetazolamide treatment (mean, 626; 95% CI, 91–1160 μmol·cm −1·h −1) and in the control tests (mean, 868; 95% CI, 652–1084 μmol·cm −1·h −1). However, acetazolamide treatment significantly decreased prostaglandin E 2-stimulated HCO 3 − secretion from 461 (95% CI, 307–615) to 222 (95% CI, 121–324) μmol·cm −1·h −1. Conclusions : Duodenal mucosal carbonic anhydrase activity has an important function in the regulation of basal and prostaglandin E 2-stimulated human duodenal mucosal bicarbonate transport.