Abstract
The mechanism(s) by which dopamine inhibits Na+-K+-ATPase activity in the renal proximal tubule is still controversial. We studied the short-term effects of dopamine on the sodium pump in rat renal proximal tubule suspensions with the 86Rb uptake method. Dopamine and the D1-like agonist, SKF81297, initially stimulated Na+-K+-ATPase activity at 5 min and subsequently inhibited it at 10 min and 20 min; the inhibition by 10 microM dopamine at 20 min was 21.3 +/- 4.5%. The inhibitory effect of dopamine on Na+-K+-ATPase activity was mimicked by thymeleatoxin (a classical protein kinase C [PKC] agonist) while Sp-8-CPT-cAMPS (a protein kinase A [PKA] agonist) had no effect. However, the combination of the PKC and PKA agonists mimicked the biphasic effects of dopamine and SKF81297. Rp-8-CPT-cAMPS (a PKA inhibitor), U-73122 (a phospholipase C inhibitor), or calphostin C (a PKC inhibitor), blocked the dopamine-mediated biphasic effects on Na+-K+-ATPase activity. It is suggested that the biphasic effects of dopamine on Na+-K+-ATPase activity (an initial stimulation and a subsequent inhibition) are transduced by activating both PKA and PKC through a D1-like receptor.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Benzazepines / pharmacology
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Cardiotonic Agents / pharmacology*
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Collagenases / pharmacology
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / drug effects
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dopamine / pharmacology*
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Dopamine Agonists / pharmacology
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Ion Transport / drug effects
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Kidney Tubules, Proximal / diagnostic imaging
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Kidney Tubules, Proximal / drug effects
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Kidney Tubules, Proximal / metabolism*
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Male
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Phorbol Esters / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Protein Kinase C / drug effects
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Protein Kinase C / metabolism
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Pyrrolidinones / pharmacology
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Radionuclide Imaging
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Rats
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Rats, Inbred WKY
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Rubidium Radioisotopes / pharmacokinetics*
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Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
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Sodium-Potassium-Exchanging ATPase / drug effects
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Sodium-Potassium-Exchanging ATPase / metabolism
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Thionucleotides / pharmacology
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Type C Phospholipases / antagonists & inhibitors
Substances
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Benzazepines
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Cardiotonic Agents
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Dopamine Agonists
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Enzyme Inhibitors
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Estrenes
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Phorbol Esters
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Rubidium Radioisotopes
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Thionucleotides
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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adenosine-3',5'-cyclic phosphorothioate
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SK&F 81297
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thymeleatoxin
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Type C Phospholipases
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Collagenases
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Sodium-Potassium-Exchanging ATPase
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Dopamine