INHIBITION OF NA,K-ATPASE ACTIVITY BY CGMP IS ISOFORM-SPECIFIC IN BRAIN ENDOTHELIAL-CELLS

cGMP has been shown to either activate or inhibit Na,K-ATPase activity , Using mouse brain endothelial cells which express both ouabain-resis tant ai and ouabain-sensitive alpha 2 and alpha 3 isoforms, we show th at cGMP reduces total Na,K-ATPase activity to about 58%, The inhibitio n 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 ox ide. cGMP-induced inhibition acts mainly on al isoforms but hardly aff ects alpha 2/alpha 3 isoforms, These data suggest that inhibition of N a,K-ATPase activity by cGMP occurs in an isoform-selective manner in b rain endothelial cells, (C) 1998 Federation of European Biochemical So cieties.