Regulation of renal Na+,K+ -ATPase and ouabain-sensitive H+,K+ -ATPase by the cyclic AMP-protein kinase A signal transduction pathway.

• Authors: Jerzy Bełtowski , Andrzej Marciniak , Grażyna Wójcicka , Dionizy Górny
• Languages of publication: EN

Abstracts

EN

We investigated the effect of the cyclic AMP-protein kinase A (PKA) signalling pathway on renal Na+,K+-ATPase and ouabain-sensitive H+,K+-ATPase. Male Wistar rats were anaesthetized and catheter was inserted through the femoral artery into the abdominal aorta proximally to the renal arteries for infusion of the investigated substances. Na+,K+-ATPase activity was measured in the presence of Sch 28080 to block ouabain-sensitive H+,K+-ATPase and improve specificity of the assay. Dibutyryl-cyclic AMP (db-cAMP) administered at a dose of 10-17 mol/kg per min and 10-6 mol/kg per min increased Na+,K+-ATPase activity in the renal cortex by 34% and 42%, respectively, and decreased it in the renal medulla by 30% and 44%, respectively. db-cAMP infused at 10-6 mol/kg per min increased the activity of cortical ouabain-sensitive H+,K+-ATPase by 33%, and medullary ouabain-sensitive H+,K+-ATPase by 30%. All the effects of db-cAMP were abolished by a specific inhibitor of protein kinase A, KT 5720. The stimulatory effect on ouabain-sensitive H+,K+-ATPase and on cortical Na+,K+-ATPase was also abolished by brefeldin A which inhibits the insertion of proteins into the plasma membranes, whereas the inhibitory effect on medullary Na+,K+-ATPase was partially attenuated by 17-octadecynoic acid, an inhibitor of cytochrome P450-dependent arachidonate metabolism. We conclude that the cAMP-PKA pathway stimulates Na+,K+-ATPase in the renal cortex as well as ouabain-sensitive H+,K+-ATPase in the cortex and medulla by a mechanism requiring insertion of proteins into the plasma membrane. In contrast, medullary Na+,K+-ATPase is inhibited by cAMP through a mechanism involving cytochrome P450-dependent arachidonate metabolites.

Keywords

EN

kidney; cyclic AMP; protein kinase A; cytochrome P450-dependent arachidonate metabolites; Na+,K+ -ATPase; H+,K+ -ATPase

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2003
• Volume: 50
• Issue: 1
• Pages: 103-114

Dates

published

2003

revised

2003-01-02

accepted

2003-02-26

received

2003-10-30

Contributors

author

Jerzy Bełtowski

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Andrzej Marciniak

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Grażyna Wójcicka

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Dionizy Górny

• Department of Pathophysiology, Medical University, Lublin, Poland

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