Influence of alpha 1-adrenergic receptor stimulation and phorbol esters on hepatic Na+/K+-ATPase activity.
The effects of the alpha 1-adrenergic agonist phenylephrine (PE) and the phorbol ester 4 beta-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 mumol/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 alpha 1-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 mumol/l) reduced 86Rb uptake and Na+/K+-ATPase and similar to PE, this inhibition was paralleled by an increase of Mg2+-ATPase activity. 4 alpha-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-sensitive 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.
Smart
J L
JL
Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Mass.
Deth
R C
RC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D010703:Phorbol Esters; D012414:Rubidium Radioisotopes; D010656:Phenylephrine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase