ArticleThe Journal of biological chemistry2009
Regulation of epithelial Na+ transport by soluble adenylyl cyclase in kidney collecting duct cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Canagliflozin Inhibits Electrogenic Na+ Transport in Mouse Cortical Collecting Duct Cells.Function (Oxford, England) · 2025Article
- The role of soluble adenylyl cyclase in sensing and regulating intracellular pH.Pflugers Archiv : European journal of physiology · 2024Review
- Molecular and biochemical characterization of the bicarbonate-sensing soluble adenylyl cyclase from a bony fish, the rainbow troutInterface focus · 2021Article
- The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility.Pflugers Archiv : European journal of physiology · 2020Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPJournal of the American Society of Nephrology : JASN · 2018Article
- Identification of a molecular pH sensor in coral.Proceedings. Biological sciences · 2017Article
- Bicarbonate-sensing soluble adenylyl cyclase is present in the cell cytoplasm and nucleus of multiple shark tissues.Physiological reports · 2017Article
- pH sensors and ion Transporters: Potential therapeutic targets for acid-base disorders.International journal of pharma research & review · 2016Article
- Soluble adenylyl cyclase in health and disease.Biochimica et biophysica acta · 2014Review
- Regulation of proximal tubule vacuolar H(+)-ATPase by PKA and AMP-activated protein kinase.American journal of physiology. Renal physiology · 2014Article
- Regulation of nephron water and electrolyte transport by adenylyl cyclases.American journal of physiology. Renal physiology · 2014Review
- Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure.American journal of physiology. Renal physiology · 2014Article
- Nonpigmented ciliary epithelial cells respond to acetazolamide by a soluble adenylyl cyclase mechanism.Investigative ophthalmology & visual science · 2014Article
- Adenylyl cyclase 4 does not regulate collecting duct water and sodium handling.Physiological reports · 2014Article
- The role of cAMP-mediated intracellular signaling in regulating Na+ uptake in zebrafish larvae.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Article
- Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin.The Journal of biological chemistry · 2013Article
- Protein kinase A-Iα regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO(2) concentrations.American journal of respiratory cell and molecular biology · 2013Article
- Adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity.Journal of the American Society of Nephrology : JASN · 2013Article
- Water absorption and bicarbonate secretion in the intestine of the sea bream are regulated by transmembrane and soluble adenylyl cyclase stimulation.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2012Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Alkalosis impairs the natriuretic response to diuretics, but the underlying mechanisms are unclear. The soluble adenylyl cyclase (sAC) is a chemosensor that mediates bicarbonate-dependent elevation of cAMP in intracellular microdomains. We hypothesized that sAC may be an important regulator of Na(+) transport in the kidney. Confocal images of rat kidney revealed specific immunolocalization of sAC in collecting duct cells, and immunoblots confirmed sAC expression in mouse cortical collecting duct (mpkCCD(c14)) cells. These cells exhibit aldosterone-stimulated transepithelial Na(+) currents that depend on both the apical epithelial Na(+) channel (ENaC) and basolateral Na(+),K(+)-ATPase. RNA interference-mediated 60-70% knockdown of sAC expression comparably inhibited basal transepithelial short circuit currents (I(sc)) in mpkCCD(c14) cells. Moreover, the sAC inhibitors KH7 and 2-hydroxyestradiol reduced I(sc) in these cells by 50-60% within 30 min. 8-Bromoadenosine-3',5'-cyclic-monophosphate substantially rescued the KH7 inhibition of transepithelial Na(+) current. Aldosterone doubled ENaC-dependent I(sc) over 4 h, an effect that was abolished in the presence of KH7. The sAC contribution to I(sc) was unaffected with apical membrane nystatin-mediated permeabilization, whereas the sAC-dependent Na(+) current was fully inhibited by basolateral ouabain treatment, suggesting that the Na(+),K(+)-ATPase, rather than ENaC, is the relevant transporter target of sAC. Indeed, neither overexpression of sAC nor treatment with KH7 modulated ENaC currents in Xenopus oocytes. ATPase and biotinylation assays in mpkCCD(c14) cells demonstrated that sAC inhibition decreases catalytic activity rather than surface expression of the Na(+),K(+)-ATPase. In summary, these results suggest that sAC regulates both basal and agonist-stimulated Na(+) reabsorption in the kidney collecting duct, acting to enhance Na(+),K(+)-ATPase activity.
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