Biphasic effects of dopamine on 86rubidium uptake in rat renal proximal tubules.
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.
Aoki
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The Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Aviles
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DH
Jose
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D017364:Collagenases / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D011877:Radionuclide Imaging; D051381:Rats; D011921:Rats, Inbred WKY; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001552:Benzazepines; D002316:Cardiotonic Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D004963:Estrenes; D010703:Phorbol Esters; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012414:Rubidium Radioisotopes; D013873:Thionucleotides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C016957:adenosine-3',5'-cyclic phosphorothioate; C067113:SK&F 81297; C080287:thymeleatoxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D017364:Collagenases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine