Activation of dopamine D1-like receptor causes phosphorylation of α1-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-teuahydro-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. (C) 2001 Elsevier Science B.V. All rights reserved.