Hormonal‐dependent recruitment of Na + ,K + ‐ATPase to the plasmalemma is mediated by PKC β and modulated by [Na + ] i

The present study demonstrates that stimulation of hormonal receptors of proximal tubule cells with the serotonin‐agonist 8‐hydroxy‐2‐(di‐n‐propylamino) tetraline (8‐OH‐DPAT) induces an augmentation of Na + ,K + ‐ATPase activity that results from the recruitment of enzyme molecules to the plasmalemma. Cells expressing the rodent wild‐type Na + ,K + ‐ATPase α‐subunit had the same basal Na + ,K + ‐ATPase activity as cells expressing the α‐subunit S11A or S18A mutants, but stimulation of Na + ,K + ‐ATPase activity was completely abolished in either mutant. 8‐OH‐DPAT treatment of OK cells led to PKC β ‐dependent phosphorylation of the α‐subunit Ser‐11 and Ser‐18 residues, and determination of enzyme activity with the S11A and S18A mutants indicated that both residues are essential for the agonist‐dependent stimulation of Na + ,K + ‐ATPase activity. When cells were treated with both dopamine and 8‐OH‐DPAT, an activation of Na + ,K + ‐ATPase was observed at basal intracellular sodium concentration (∼9 m M ), and this activation was gradually reduced and became a significant inhibition as the concentration of intracellular sodium gradually increased from 9 to 19 m M . Thus, besides the antagonistic effects of dopamine and 8‐OH‐DPAT, intracellular sodium modulates whether an activation or an inhibition of Na + ,K + ‐ATPase is produced.British Journal of Pharmacology (2002) 137 , 1380–1386. doi: 10.1038/sj.bjp.0704962