ArticleThe Journal of biological chemistry2010
Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 84 citations in OpenAlex.
- Review
- Histamine regulates the activity and the expression of the NaInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Role of Angiotensin II Type 1a Receptor (AT1aR) of Renal Tubules in Regulating Inwardly Rectifying Potassium Channels 4.2 (Kir4.2), Kir4.1, and Epithelial NaHypertension (Dallas, Tex. : 1979) · 2024Article
- Inherited Fanconi syndrome.World journal of pediatrics : WJP · 2023Review
- Great debate: in patients with decompensated heart failure, acetazolamide in addition to loop diuretics is the first choice.European heart journal · 2023 · on this mapArticle
- Dietary sodium enhances the expression of SLC4 family transporters, IRBIT, L-IRBIT, and PP1 in rat kidney: Insights into the molecular mechanism for renal sodium handling.Frontiers in physiology · 2023Article
- The NaFrontiers in physiology · 2022Review
- Crosstalk between Sodium-Glucose Cotransporter Inhibitors and Sodium-Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases.International journal of molecular sciences · 2021Review
- Article
- New Insights into the Critical Importance of Intratubular NaCurrent hypertension reports · 2021Review
- Both IRBIT and long-IRBIT bind to and coordinately regulate ClScientific reports · 2021Article
- Angiotensin II and Angiotensin Receptors 1 and 2-Multifunctional System in Cells Biology, What Do We Know?Cells · 2021Review
- IRBIT activates NBCe1-B by releasing the auto-inhibition module from the transmembrane domain.The Journal of physiology · 2021Article
- Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells.Pharmaceutics · 2020Article
- Depotentiation depends on IPLearning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Proximal Tubule-Specific Deletion of the NHE3 (NaHypertension (Dallas, Tex. : 1979) · 2019Article
- Effects of ATRAP in Renal Proximal Tubules on Angiotensin-Dependent Hypertension.Journal of the American Heart Association · 2019Article
- Genetic and genomic evidence for an important role of the NaPhysiological genomics · 2019Review
- Hyperglycemia promotes microvillus membrane expression of DMT1 in intestinal epithelial cells in a PKCα-dependent manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Angiotensin II (ANG II) stimulates renal tubular reabsorption of NaCl by targeting Na(+)/H(+) exchanger NHE3. We have shown previously that inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concentration ([Ca(2+)](i)). In this study, we investigated the role of IRBIT in mediating NHE3 activation by ANG II. IRBIT is abundantly expressed in the proximal tubules where NHE3 is located. ANG II at physiological concentrations stimulates NHE3 transport activity in a model proximal tubule cell line. ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overexpression of IRBIT enhanced the effect of ANG II on NHE3. ANG II transiently increased binding of IRBIT to NHE3 at 5 min but became dissociated by 45 min. In comparison, it took at least 15 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression. The stimulation of NHE3 by ANG II was dependent on changes in [Ca(2+)](i) and Ca(2+)/calmodulin-dependent protein kinases II. Inhibition of CaMKII completely blocked the ANG II-induced binding of IRBIT to NHE3 and the increase in NHE3 surface abundance. Several serine residues of IRBIT are thought to be important for IRBIT binding. Mutations of Ser-68, Ser-71, and Ser-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity. In conclusion, our current findings demonstrate that IRBIT is critically involved in mediating activation of NHE3 by ANG II via a Ca(2+)/calmodulin-dependent protein kinases II-dependent pathway.
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