Cardiac Na+,K+-ATPase isoenzymes: sensitivity to prednisolone bisguanylhydrazone.
Prednisolone-3,20-bisguanylhydrazone (PBGH), a steroid derivative, has been shown to inhibit Na+,K+-ATPase isolated from guinea-pig heart or kidney in concentrations significantly lower than those required to inhibit the enzyme obtained from other sources. Because Na+,K+-ATPases obtained from guinea-pig heart or kidney are predominantly of the alpha isoform, the hypothesis that PBGH selectively inhibits the alpha isoform over alpha (+) isoform of the enzyme was tested. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the enzyme preparations revealed the presence of only the higher mobility, alpha isoform in guinea-pig heart and ferret kidney, whereas those from guinea-pig brain, dog brain and ferret heart showed both high and low mobility isoforms corresponding to alpha and alpha (+) isoforms. Na+,K+-ATPase obtained from the guinea-pig heart was most sensitive to PBGH and those isolated from ferret heart or ferret kidney had the lowest sensitivity. Enzyme preparations obtained from dog brain, dog heart or guinea-pig brain had intermediate sensitivity. This spectrum of enzyme sensitivity to PBGH was markedly different from that to ouabain. In ferret heart Na+,K+-ATPase, a low concentration of PBGH preferentially inhibited [3H]ouabain binding to the high affinity ouabain binding sites (alpha(+) isoform). These results indicate that PBGH is not a specific inhibitor of the alpha isoforms of Na+,K+-ATPase. Affinity of the enzyme for PBGH is determined by the species and tissue rather than isoforms of Na+,K+-ATPase.
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Leung
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Akera
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D000818:Animals; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005289:Ferrets; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013045:Species Specificity
D007527:Isoenzymes; D010042:Ouabain; C017938:prednisolone-3,20-bisguanylhydrazone; D011239:Prednisolone; D000254:Sodium-Potassium-Exchanging ATPase