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J Biol Chem
2009 Feb 27;2849:5774-83. doi: 10.1074/jbc.M805501200.
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Regulation of epithelial Na+ transport by soluble adenylyl cyclase in kidneycollecting duct cells.
Hallows KR, Wang H, Edinger RS, Butterworth MB, Oyster NM, Li H, Buck J, Levin LR, Johnson JP, Pastor-Soler NM.
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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.
Bens,
Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line.
1999, Pubmed
Bens,
Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line.
1999,
Pubmed Bhalla,
Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ.
2006,
Pubmed Bosch,
Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog.
1977,
Pubmed Breton,
Tetanus toxin-mediated cleavage of cellubrevin inhibits proton secretion in the male reproductive tract.
2000,
Pubmed Breton,
Proton secretion in the male reproductive tract: involvement of Cl--independent HCO-3 transport.
1998,
Pubmed Brown,
Antigen retrieval in cryostat tissue sections and cultured cells by treatment with sodium dodecyl sulfate (SDS).
1996,
Pubmed Brown,
The ins and outs of aquaporin-2 trafficking.
2003,
Pubmed Buck,
Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals.
1999,
Pubmed Bundey,
Discrete intracellular signaling domains of soluble adenylyl cyclase: camps of cAMP?
2004,
Pubmed Butterworth,
Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.
2005,
Pubmed Butterworth,
Regulation of the epithelial sodium channel by membrane trafficking.
2009,
Pubmed Carattino,
Epithelial sodium channel inhibition by AMP-activated protein kinase in oocytes and polarized renal epithelial cells.
2005,
Pubmed
,
Xenbase Cass,
The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B.
1970,
Pubmed Chen,
Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor.
2000,
Pubmed Cheng,
PKA-mediated phosphorylation and inhibition of Na(+)-K(+)-ATPase in response to beta-adrenergic hormone.
1997,
Pubmed Cortes,
The gamma subunit of Na+, K+-ATPase: role on ATPase activity and regulatory phosphorylation by PKA.
2006,
Pubmed de Rooij,
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP.
1998,
Pubmed Erlij,
Forskolin increases apical sodium conductance in cultured toad kidney cells (A6) by stimulating membrane insertion.
1999,
Pubmed Farrell,
Somatic 'soluble' adenylyl cyclase isoforms are unaffected in Sacy tm1Lex/Sacy tm1Lex 'knockout' mice.
2008,
Pubmed Forbush,
Assay of Na,K-ATPase in plasma membrane preparations: increasing the permeability of membrane vesicles using sodium dodecyl sulfate buffered with bovine serum albumin.
1983,
Pubmed Franzin,
Structures of the FXYD regulatory proteins in lipid micelles and membranes.
2007,
Pubmed Geng,
Cloning and characterization of the human soluble adenylyl cyclase.
2005,
Pubmed Gonin,
Cyclic AMP increases cell surface expression of functional Na,K-ATPase units in mammalian cortical collecting duct principal cells.
2001,
Pubmed Harvey,
Rapid responses to aldosterone in the kidney and colon.
2008,
Pubmed Hess,
The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization.
2005,
Pubmed Jaiswal,
Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa.
2003,
Pubmed Kamenetsky,
Molecular details of cAMP generation in mammalian cells: a tale of two systems.
2006,
Pubmed Kleizen,
Regulated trafficking of the CFTR chloride channel.
2000,
Pubmed Kleyman,
Arginine vasopressin and forskolin regulate apical cell surface expression of epithelial Na+ channels in A6 cells.
1994,
Pubmed
,
Xenbase Lewis,
Nystatin as a probe for investigating the electrical properties of a tight epithelium.
1977,
Pubmed Litvin,
Kinetic properties of "soluble" adenylyl cyclase. Synergism between calcium and bicarbonate.
2003,
Pubmed Loon,
Mild metabolic alkalosis impairs the natriuretic response to bumetanide in normal human subjects.
1998,
Pubmed Masilamani,
Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney.
1999,
Pubmed Mittag,
Bicarbonate-activated adenylyl cyclase in fluid-transporting tissues.
1993,
Pubmed Mohan,
Differential current decay profiles of epithelial sodium channel subunit combinations in polarized renal epithelial cells.
2004,
Pubmed Nelson,
Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56-kilodalton subunit in renal intercalated cells.
1992,
Pubmed Palmer,
Modulation of apical Na permeability of the toad urinary bladder by intracellular Na, Ca, and H.
1985,
Pubmed Pastor-Soler,
Alkaline pH- and cAMP-induced V-ATPase membrane accumulation is mediated by protein kinase A in epididymal clear cells.
2008,
Pubmed Pastor-Soler,
Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling.
2003,
Pubmed Paunescu,
Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells.
2008,
Pubmed Pochynyuk,
Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides.
2006,
Pubmed Ramos,
Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells.
2008,
Pubmed Rokaw,
Rapamycin inhibits protein kinase C activity and stimulates Na+ transport in A6 cells.
1996,
Pubmed
,
Xenbase Schmid,
Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP.
2007,
Pubmed Snyder,
cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2.
2004,
Pubmed Steegborn,
A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen.
2005,
Pubmed Stessin,
Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1.
2006,
Pubmed Stockand,
Toward Understanding the Role of Methylation in Aldosterone-Sensitive Na(+) Transport.
2000,
Pubmed Summa,
Isoform specificity of human Na(+), K(+)-ATPase localization and aldosterone regulation in mouse kidney cells.
2004,
Pubmed Therien,
Mechanisms of sodium pump regulation.
2000,
Pubmed USSING,
Active transport of sodium as the source of electric current in the short-circuited isolated frog skin.
1951,
Pubmed Wang,
Regulation of CFTR channels by HCO(3)--sensitive soluble adenylyl cyclase in human airway epithelial cells.
2005,
Pubmed Weber,
Capacitance measurements reveal different pathways for the activation of CFTR.
1999,
Pubmed
,
Xenbase Welling,
Aldosterone-mediated Na/K-ATPase expression is alpha 1 isoform specific in the renal cortical collecting duct.
1993,
Pubmed Wetzel,
Immunocytochemical localization of Na-K-ATPase alpha- and gamma-subunits in rat kidney.
2001,
Pubmed Wu,
Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones.
2006,
Pubmed Young,
"Soluble" adenylyl cyclase-generated cyclic adenosine monophosphate promotes fast migration in PC12 cells.
2008,
Pubmed Zippin,
Bicarbonate-responsive "soluble" adenylyl cyclase defines a nuclear cAMP microdomain.
2004,
Pubmed Zippin,
Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains.
2003,
Pubmed
