ArticleThe Journal of clinical investigation2009
IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
77 citing papers in PubMed, 137 citations in OpenAlex.
- S-adenosylhomocysteine hydrolase-like protein 1 deficiency resulted in stronger inflammation reaction in acute pancreatitis.Journal of gastroenterology · 2026Article
- Deciphering the multi-site phos-code of IRBIT underlying its binding to IPCommunications biology · 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
- Multiple cAMP/PKA complexes at the STIM1 ER/PM junction specified by E-Syt1 and E-Syt2 reciprocally gates ANO1 (TMEM16A) via CaNature communications · 2025Article
- Downregulation of solute carrier family 4 members 4 as a biomarker for colorectal cancer.Discover oncology · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma.Theranostics · 2025Article
- Bicarbonate secretion and acid/base sensing by the intestine.Pflugers Archiv : European journal of physiology · 2024Review
- Unity Is Strength: The Mutual Alliance between CFTR and SLC26A6 as Therapeutic Opportunity in Cystic Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity.Biology direct · 2023Article
- Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1.Pflugers Archiv : European journal of physiology · 2023Article
- Inhibition of the sodium-dependent HCOeLife · 2022Article
- Review
- Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge.International journal of molecular sciences · 2021Review
- Both IRBIT and long-IRBIT bind to and coordinately regulate ClScientific reports · 2021Article
- Carbonic anhydrases enhance activity of endogenous Na-H exchangers and not the electrogenic Na/HCOThe Journal of physiology · 2020Article
- Advances in CaExperimental and therapeutic medicine · 2020Review
- Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells.Pharmaceutics · 2020Article
- CaCold Spring Harbor perspectives in biology · 2020Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Fluid and HCO3- secretion are vital functions of secretory epithelia. In most epithelia, this entails HCO3- entry at the basolateral membrane, mediated by the Na+-HCO3- cotransporter, pNBC1, and exit at the luminal membrane, mediated by a CFTR-SLC26 transporters complex. Here we report that the protein IRBIT (inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3), a previously identified activator of pNBC1, activates both the basolateral pNBC1 and the luminal CFTR to coordinate fluid and HCO3- secretion by the pancreatic duct. We used video microscopy and ion selective microelectrodes to measure fluid secretion and Cl- and HCO3- concentrations in cultured murine sealed intralobular pancreatic ducts. Short interference RNA-mediated knockdown of IRBIT markedly inhibited ductal pNBC1 and CFTR activities, luminal Cl- absorption and HCO3- secretion, and the associated fluid secretion. Single-channel measurements suggested that IRBIT regulated CFTR by reducing channel mean close time. Furthermore, expression of IRBIT constructs in HEK cells revealed that activation of pNBC1 required only the IRBIT PEST domain, while activation of CFTR required multiple IRBIT domains, suggesting that IRBIT activates these transporters by different mechanisms. These findings define IRBIT as a key coordinator of epithelial fluid and HCO3- secretion and may have implications to all CFTR-expressing epithelia and to cystic fibrosis.
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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.