Vanadyl ions stimulate K⁺ uptake into isolated perfused rat liver via the Na⁺/K⁺-pump by a tyrosine kinase-dependent mechanism

Vanadium salts mimic most metabolic effects of insulin in vitro. We report here that vanadyl sulfate (VOSO₄) and sodium vanadate (NaVO₃) stimulate net K⁺ uptake in isolated perfused rat liver. Stimulation was evident at low concentrations of vanadyl ions (range 1-20 μM) and occurred within minutes following the addition of VOSO₄. By comparison with VOSO₄, insulin had less of a stimulatory effect on K⁺ uptake. Ouabain prevented the activating effect of VOSO₄ on K⁺ uptake. Following 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 via the Na⁺/K⁺-ATPase was stimulated by vanadyl ions. An indirect mechanism-due to changes in [Na⁺](i) can be excluded. The tyrosine kinase inhibitor genistein was found to inhibit stimulation of K⁺ by vanadyl and vanadate ions which are known inhibitors of phosphotyrosine phosphatases. We conclude that stimulation of active K⁺ influx involves a tyrosine kinase. Possible mechanisms include phosphorylation at tyrosine residues and direct activation of the Na⁺/K⁺-ATPase, or phosphorylation of other proteins that regulate the activity or number of pumps in the cells.