Activation of dopamine D(1)-like receptor causes phosphorylation of alpha(1)-subunit of Na(+),K(+)-ATPase in rat renal proximal tubules.
Dopamine causes inhibition of Na(+),K(+)-ATPase activity via activation of dopamine D(1)-like receptors. It is the phosphorylation of Serine(18) of the alpha(1)-subunit of Na(+),K(+)-ATPase which results in the inhibition of the enzyme activity; however, such a phosphorylation by dopamine D(1)-like receptor agonist has not been demonstrated in the proximal tubules. We show here by immunoprecipitation and detection with phosphoserine antibody that SKF 38393, a dopamine D(1)-like receptor agonist, causes phosphorylation of the alpha(1)-subunit of Na(+),K(+)-ATPase. The effect of (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride, SKF 38393, is blocked by R(+)-7-choro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride, SCH 23390, a dopamine D(1)-like receptor antagonist, and staurosporin, a protein kinase C inhibitor. The phosphorylation is also increased by phorbol 12-13 dibutyrate ester. However, Rp-cAMP triethylamine, an inhibitor of protein kinase A, does not affect the SKF 38393-mediated phosphorylation of Na(+),K(+)-ATPase. Therefore, these results provide the evidence that dopamine D(1)-like receptor activation causes phosphorylation of the alpha(1)-subunit of Na(+),K(+)-ATPase in renal proximal tubules via protein kinase C pathway.
Asghar
M
M
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, 77204-5515, Houston, TX, USA.
Hussain
T
T
Lokhandwala
M F
MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002460:Cell Line; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D017447:Receptors, Dopamine D1; D015240:Phorbol 12,13-Dibutyrate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate