VANADYL IONS STIMULATE K-PERFUSED RAT-LIVER VIA THE NA+( UPTAKE INTO ISOLATED)K+-PUMP BY A TYROSINE KINASE-DEPENDENT MECHANISM/

Vanadium salts mimic most metabolic effects of insulin in vitro. We re port here that vanadyl sulfate (VOSO4,) and sodium vanadate (NaVO3,) s timulate net K+ uptake in isolated perfused rat liver. Stimulation was evident at low concentrations of vanadyl ions (range 1-20 mu M) and o ccurred within minutes following the addition of VOSO4. By comparison with VOSO4,, insulin had less of a stimulatory effect on K+ uptake. Ou abain prevented the activating effect of VOSO4, on K+ uptake. Followin g a VOSO4 challenge, measured intracellular Na+ concentration ([Na+](i )) fell (control, 17.1 +/- 1.2; VOSO4-treated, 13.0 +/- 1.1 mmol.g(-1) wet weight, P = 0.027). The results indicate that active K+ uptake vi a the Na+/K+-ATPase was stimulated by vanadyl ions. An indirect mechan ism due to changes in [Na+](i), can be excluded. The tyrosine kinase i nhibitor genistein was found to inhibit stimulation of K+ by vanadyl a nd vanadate ions which are known inhibitors of phosphotyrosine phospha tases. We conclude that stimulation of active K+ influx involves a tyr osine kinase. Possible mechanisms include phosphorylation at tyrosine residues and direct activation of the Na+/K+-ATPase, or phosphorylatio n of other proteins that regulate the activity or number of pumps in t he cells.