HUMAN PROXIMAL DUODENAL ALKALINE SECRETION IS MEDIATED BY CL- HCO3- EXCHANGE AND HCO3- CONDUCTANCE/

The proximal duodenal epithelium secretes bicarbonate into an adherent mucus layer, thereby protecting the mucosa from injury by gastric aci d and pepsin. While bicarbonate secretion is stimulated and inhibited by a number of agonists and antagonists, the apical anion transport pa thways have not been addressed fully. The objective was to assess if a pical Cl-/HCO3- exchange and Cl-:HCO3- conductance are involved in duo denal mucosal bicarbonate secretion (DMBS). In healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with either saline o r 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate sec retion and transepithelial potential difference (PD) were stimulated b y either PGE(2) or the phosphodiesterase inhibitor theophylline to inc rease cyclic AMP. Luminal DIDS abolished PGE(2)-stimulated DMBS, yet h ad no effect on the increase in PD and failed to significantly alter t heophylline-induced DMBS and PD. Therefore, in human proximal duodenum , it appears that PGE(2) and cAMP activate distinct HCO3- transport pa thways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS- insensitive HCO3- conductance.