Different mechanisms of renal Na-K-ATPase regulation by dopamine in the proximal and distal nephron.
We reported a novel intracellular mechanism of renal Na-K-ATPase regulation by dopamine (DA) in the rat cortical collecting duct (CCD), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). In the present experiments we determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limbs (MTAL), DA and other cAMP agonists inhibited Na-K-ATPase activity, an effect that was abolished by PKA inhibitor IP20, but various protein kinase C (PKC) activators did not, analogous to our previous findings in CCD. In sharp contrast, DA inhibition on Na-K-ATPase in the proximal convoluted tubule (PCT) was reproduced by PKC agonists. These effects was blocked by PKC inhibitor staurosporine, but not by IP20. Mepacrine, a PLA2 inhibitor, reversed the pump effect of all agents, and arachidonic acid (AA) produced a dose-dependent pump inhibition, in all three nephron segments. We conclude that the intracellular mechanisms of Na-K-ATPase regulation by dopamine differ in the proximal and distal nephron, as they involve stimulation of PKA in MTAL and CCD, and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2 and AA release in both regions of the nephron.
First Department of Internal Medicine, St. Mariannna University School of Medicine, Kawasaki, Japan.
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Satoh
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Ominato
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Katz
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007679:Kidney Medulla / Q000201:enzymology; D007686:Kidney Tubules, Distal / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D018818:Fenoldopam; D004298:Dopamine