In vitro inhibition of Na-K-ATPase by trace metals: relation to renal and cardiovascular damage.
The potential role of trace metals in the pathogenesis of various disease states, especially of renal and cardiovascular disease, has been recognized increasingly. Moreover, altered membrane transport was recently incriminated to play a role in renal tubular syndromes, such as the Fanconi syndrome, as well as in the pathogenesis of volume dependent hypertension. We therefore investigated the possible in vitro effects of various trace metals on Na-K-ATPase, the biochemical correlate of active cellular transmembrane sodium and sodium-dependent transport. To more closely mimic the in vivo situation, we deliberately chose as enzyme source renal tissue homogenate, which may contain protective agents. Under these experimental conditions, the metals studied inhibited the enzyme quantitatively in the following order: Hg greater than Pb greater than Cd greater than Ur greater than Cu greater than Zn greater than Mn greater than Ba greater than Ni greater than Sr. Enzyme kinetic studies showed that Hg, Pb, and Cd competitively, and Cu noncompetitively, inhibited the enzyme. In general, Mg-ATPase was significantly less sensitive to the trace metals. Accumulation of these metals may present serious health hazards by producing a general defect in cell membrane transport. From the other metals studied, i.e., Mn, Ba, Ni and Sr, some may have toxic effects via other mechanisms, whereas some may exert a protective role against toxicity of other agents including metal ions.
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007854:Lead / Q000378:metabolism / Q000494:pharmacology; D008628:Mercury / Q000378:metabolism / Q000494:pharmacology; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014131:Trace Elements / Q000378:metabolism / Q000494:pharmacology*
D014131:Trace Elements; D002104:Cadmium; D007854:Lead; D010042:Ouabain; D003300:Copper; D000254:Sodium-Potassium-Exchanging ATPase; D008628:Mercury; D011188:Potassium