title: Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and HCO3- conductance.
abstract: The proximal duodenal epithelium secretes bicarbonate into an adherent mucus layer, thereby protecting the mucosa from injury by gastric acid and pepsin. While bicarbonate secretion is stimulated and inhibited by a number of agonists and antagonists, the apical anion transport pathways have not been addressed fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3- conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate secretion and transepithelial potential difference (PD) were stimulated by either PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP. Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore, in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3- transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS-insensitive HCO3- conductance.
authors.affiliation: Division of Gastroenterology, UCSD Medical Center, University of California San Diego, 92103, USA.
authors.forename: L
authors.initials: L
authors.lastname: Nyberg
authors.forename: V
authors.initials: V
authors.lastname: Pratha
authors.forename: D L
authors.initials: DL
authors.lastname: Hogan
authors.forename: R C
authors.initials: RC
authors.lastname: Rapier
authors.forename: M A
authors.initials: MA
authors.lastname: Koss
authors.forename: J I
authors.initials: JI
authors.lastname: Isenberg
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000328:Adult; D017920:Antiporters; D001639:Bicarbonates / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000494:pharmacology
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid