ArticleThe Journal of clinical investigation2000
Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 70 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- Pancreatitis: correcting CFTR expression and function as a promising effective treatment.Frontiers in physiology · 2026Review
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Advances in research on the regulatory mechanism of NHE1 in tumors.Oncology letters · 2021Review
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Functional identification of protein phosphatase 1-binding consensus residues in NBCe1-B.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- The Balance of [Formula: see text] Secretion vs. Reabsorption in the Endometrial Epithelium Regulates Uterine Fluid pH.Frontiers in physiology · 2018Article
- Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Differential expression of Na+/H+-exchanger (NHE-1, 2, and 4) proteins and mRNA in rodent's uterus under sex steroid effect and at different phases of the oestrous cycle.BioMed research international · 2013Article
- Transepithelial bicarbonate secretion: lessons from the pancreas.Cold Spring Harbor perspectives in medicine · 2012Article
- Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion.Physiological reviews · 2012Review
- IRBIT: it is everywhere.Neurochemical research · 2011Review
- Pancreatic bicarbonate secretion involves two proton pumps.The Journal of biological chemistry · 2011Article
- CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners.Integrative biology : quantitative biosciences from nano to macro · 2010Review
- Ducts isolated from the pancreas of CFTR-null mice secrete fluid.Pflugers Archiv : European journal of physiology · 2009Article
- Reduced NHE3-mediated Na+ absorption increases survival and decreases the incidence of intestinal obstructions in cystic fibrosis mice.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
- IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct.The Journal of clinical investigation · 2009Article
- Bicarbonate secretion by rat bile duct brush cells indicated by immunohistochemical localization of CFTR, anion exchanger AE2, Na+/HCO3 -cotransporter, carbonic anhydrase II, Na+/H+ exchangers NHE1 and NHE3, H+/K+-ATPase, and Na+/K+-ATPase.Medical molecular morphology · 2006Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
To study the roles of Na(+)-dependent H(+) transporters, we characterized H(+) efflux mechanisms in the pancreatic duct in wild-type, NHE2(-/-), and NHE3(-/-) mice. The pancreatic duct expresses NHE1 in the basolateral membrane, and NHE2 and NHE3 in the luminal membrane, but does not contain NHE4 or NHE5. Basolateral Na(+)-dependent H(+) efflux in the microperfused duct was inhibited by 1.5 microM of the amiloride analogue HOE 694, consistent with expression of NHE1, whereas the luminal activity required 50 microM HOE 694 for effective inhibition, suggesting that the efflux might be mediated by NHE2. However, disruption of NHE2 had no effect on luminal transport, while disruption of the NHE3 gene reduced luminal Na(+)-dependent H(+) efflux by approximately 45%. Notably, the remaining luminal Na(+)-dependent H(+) efflux in ducts from NHE3(-/-) mice was inhibited by 50 microM HOE 694. Hence, approximately 55% of luminal H(+) efflux (or HCO(3)(-) influx) in the pancreatic duct is mediated by a novel, HOE 694-sensitive, Na(+)-dependent mechanism. H(+) transport by NHE3 and the novel transporter is inhibited by cAMP, albeit to different extents. We propose that multiple Na(+)-dependent mechanisms in the luminal membrane of the pancreatic duct absorb Na(+) and HCO(3)(-) to produce a pancreatic juice that is poor in HCO(3)(-) and rich in Cl(-) during basal secretion. Inhibition of the transporters during stimulated secretion aids in producing the HCO(3)(-)-rich pancreatic juice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.