Influence of α₁-adrenergic receptor stimulation and phorbol esters on hepatic Na⁺/K⁺-ATPase activity

The effects of the α1-adrenergic agoinst phenylephrine (PE) and the phorbol ester 4β-phorbolmyristate-acetate (PMA) on sodium pump function were studied in the rat liver. In order to distinguish between direct and indirect influences, ouabain-sensitive 86Rb uptake by intact liver slices was compared with ouabain-sensitive Na+/K+-ATPase activity in plasma membranes isolated from PE and PMA-perfused livers. At a buffer Ca2+ level of 2.5 mmol/l, PE (10 μmol/l) caused an initial stimulation of both 86Rb uptake and Na+/K+-ATPase activity followed at 5 min by a decrease in both activities. Both actions were blocked by the α1-antagonist prazosin. The decrease in ouabain-sensitive Na+/K+-ATPase was paralleled by an increase in Mg2+-ATPase activity. At a Ca2+ level of 1.5 mmol/l, PE stimulation of 86Rb uptake and Na+/K+-ATPase was sustained, and the inhibitory component was not expressed. PMA (4 μmol/l) reduced 86Rb uptake and Na+/K+-ATPase and similar to PE, this inhibition was paralleled by an increase of Mg2+-ATPase activity. 4α-PMA, which does not activate protein kinase C, failed to influence 86Rb uptake or Na+/K+-ATPase. These results demonstrate that PE and PMA effects on ouabain-sensititve 86Rb uptake are preserved in isolated membranes, indicating a direct influence on the Na+/K+-ATPase. A role for protein kinase C in modulating sodium pump activity is suggested.