title: Inhibition of Na,K-ATPase activity by cGMP is isoform-specific in brain endothelial cells.
abstract: cGMP has been shown to either activate or inhibit Na,K-ATPase activity. Using mouse brain endothelial cells which express both ouabain-resistant alpha1 and ouabain-sensitive alpha2 and alpha3 isoforms, we show that cGMP reduces total Na,KATPase activity to about 58%. The inhibition is prevented by the protein kinase G (PKG)-specific inhibitor KT5823, indicating that cGMP-mediated activation of PKG leads to inhibition of the pump. A similar extent of inhibition is obtained with nitric oxide. cGMP-induced inhibition acts mainly on alpha1 isoforms but hardly affects alpha2/alpha3 isoforms. These data suggest that inhibition of Na,K-ATPase activity by cGMP occurs in an isoform-selective manner in brain endothelial cells.
authors.affiliation: Biochemistry I, Swiss Federal Institute of Technology, ETH Zentrum, Zürich.
authors.forename: L
authors.initials: L
authors.lastname: Pontiggia
authors.forename: K
authors.initials: K
authors.lastname: Winterhalter
authors.forename: S M
authors.initials: SM
authors.lastname: Gloor
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002560:Cerebrovascular Circulation; D006152:Cyclic GMP / Q000494:pharmacology*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D011994:Recombinant Proteins; C073601:KT 5823; D009569:Nitric Oxide; D010042:Ouabain; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP