Acetazolamide inhibits basal and stimulated HCO3- secretion in the human proximal duodenum.
OBJECTIVE
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 E2- 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 E2. 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 HCO3- secretion and basal transmucosal potential difference. After luminal acidification, duodenal mucosal bicarbonate increased significantly after both acetazolamide treatment (mean, 626; 95% CI, 91-1160 mumol.cm-1.h-1) and in the control tests (mean, 868; 95% CI, 652-1084 mumol.cm-1.h-1). However, acetazolamide treatment significantly decreased prostaglandin E2-stimulated HCO3- secretion from 461 (95% CI, 307-615) to 222 (95% CI, 121-324) mumol.cm-1.h-1.


CONCLUSIONS
Duodenal mucosal carbonic anhydrase activity has an important function in the regulation of basal and prostaglandin E2-stimulated human duodenal mucosal bicarbonate transport.
Knutson
T W
TW
Division of Gastroenterology, University of California at San Diego.
Koss
M A
MA
Hogan
D L
DL
Isenberg
J I
JI
Knutson
L
L
D000086:Acetazolamide / Q000494:pharmacology*; D000328:Adult; D001639:Bicarbonates / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D006859:Hydrogen; D015232:Dinoprostone; D000086:Acetazolamide