Secretion of bicarbonate from epithelial cells is considered to be the primary mechanism by which the duodenal mucosa is protected from acid-related injury. Against this view is the finding that patients with cystic fibrosis, who have impaired duodenal bicarbonate secretion, are paradoxically protected from developing duodenal ulcers. Therefore, we hypothesized that epithelial cell intracellular pH regulation, rather than secreted extracellular bicarbonate, was the principal means by which duodenal epithelial cells are protected from acidification and injury. Using a novel in vivo microscopic method, we have measured bicarbonate secretion and epithelial cell intracellular pH (pHi), and we have followed cell injury in the presence of the anion transport inhibitor DIDS and the Cl– channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). DIDS and NPPB abolished the increase of duodenal bicarbonate secretion following luminal acid perfusion. DIDS decreased basal pHi, whereas NPPB increased pHi; DIDS further decreased pHi during acid challenge and abolished the pHi overshoot over baseline observed after acid challenge, whereas NPPB attenuated the fall of pHi and exaggerated the overshoot. Finally, acid-induced epithelial injury was enhanced by DIDS and decreased by NPPB. The results support the role of intracellular bicarbonate in the protection of duodenal epithelial cells from luminal gastric acid.
Yasutada Akiba, Osamu Furukawa, Paul H. Guth, Eli Engel, Igor Nastaskin, Pejvak Sassani, Ramanath Dukkipatis, Alexander Pushkin, Ira Kurtz, Jonathan D. Kaunitz
Usage data is cumulative from August 2023 through August 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 283 | 35 |
77 | 22 | |
Figure | 147 | 19 |
Table | 25 | 0 |
Citation downloads | 23 | 0 |
Totals | 555 | 76 |
Total Views | 631 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.