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 dopa mine D-1-like receptors. It is the phosphorylation of Serine(18) of the alp ha (1)-subunit of Na+,K+-ATPase which results in the inhibition of the enzy me 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 3839 3, a dopamine D-1-like receptor agonist, causes phosphorylation of the alph a (1)-subunit of Na+,K+-ATPase. The effect of (+/-)-1-phenyl-2,3,4,5-tetrah ydro-(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 hyd rochloride. SCH 23390, a dopamine D-1-like receptor antagonist, and stauros porin, a protein kinase C inhibitor. The phosphorylation is also increased by phorbol 12-13 dibutyrate eater. However. Rp-cAMP triethylamine. an inhib itor of protein kinase A, does not affect the SKF 38393-mediated phosphoryl ation 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.