Vanadate uptake and inhibition of the sodium pump in perfused dog liver.
Although vanadate is a potent inhibitor of the (Na + K)-ATPase, few in vivo effects directly related to the inhibition of the sodium pump have been reported. In order to demonstrate a possible inhibition of the hepatocyte sodium pump, vanadate was administered at millimolar concentration during perfusion of isolated dog livers. In contrast to the marked inhibition produced by ouabain in this preparation, vanadate seems ineffective as it modified neither the intra- or extracellular Na and K concentrations nor the membrane potential. Changes in these parameters suggestive of an inhibition of the sodium pump were only obtained when vanadate was administered after a reduction of the osmolarity of the perfusing fluid to 2/3 of its initial value. The effect of hypotonicity seems related to the cellular swelling it produces and not to changes in extracellular sodium concentrations: inhibition of the sodium pump is not obtained when part of the sodium chloride is replaced by sucrose without changing the osmolarity. As the uptake of Na3 48VO4 is markedly increased by the reduction of osmolarity, it is proposed that the intracellular concentration of vanadate does not reach the level necessary to inhibit the sodium pump due to the balance between uptake and inactivation, under normal conditions. Cellular swelling increases the membrane permeability allowing a higher concentration of vanadate and a subsequent inhibition of the sodium pump.
D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D004285:Dogs; D008099:Liver / Q000201:enzymology; D008564:Membrane Potentials / Q000187:drug effects; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014638:Vanadates; D014639:Vanadium / Q000378:metabolism* / Q000494:pharmacology
D014639:Vanadium; D014638:Vanadates; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium