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 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.
Nyberg
L
L
Division of Gastroenterology, UCSD Medical Center, University of California San Diego, 92103, USA.
Pratha
V
V
Hogan
D L
DL
Rapier
R C
RC
Koss
M A
MA
Isenberg
J I
JI
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
D017920:Antiporters; D001639:Bicarbonates; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid