D(1A) dopamine receptor stimulation inhibits Na⁺/K⁺-ATPase activity through protein kinase A

We stably expressed the rat D(1A) dopamine receptor in mouse fibroblast LTK^- cells and obtained specific ligand binding and functional activity characteristic of the D(1A) dopamine receptor coupled to stimulation of adenylyl cyclase. In the transfected cells, the selective D₁ agonist fenoldopam caused a concentration-dependent inhibition of Na⁺/K⁺-ATPase activity, achieving maximum inhibition of ~30%. The latter was abolished by the selective D₁ antagonist (+)-SCH 23390 and by the specific protein kinase A inhibitor protein kinase inhibitor-(6-22) amide. In the nontransfected cells, fenoldopam did not affect Na⁺/K⁺-ATPase activity. 8- Chlorophenylthio-cAMP inhibited Na⁺/K⁺-ATPase activity in both transfected and nontransfected cells; this effect was blocked by protein kinase inhibitor-(6-22). These results indicate that the inhibition of Na⁺/K⁺- ATPase activity induced by agonist occupancy of D(1A) receptors is mediated by protein kinase A.