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ACS Omega. 2017 Jul 31;2(7):3610-3615. doi: 10.1021/acsomega.7b00591. Epub 2017 Jul 13.

Comparison of Digitalis Sensitivities of Na+/K+-ATPases from Human and Pig Kidneys.

Author information

1
Department Biochemistry & Cancer Biology, College of Medicine & Life Sciences, University of Toledo, 3000 Arlington Avenue, MS 1010, Toledo, Ohio 43614, United States.
2
Laboratory of Cardiovascular Science, National Institute of Aging, National Institutes of Health, Baltimore, Maryland 21224, United States.
3
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia.

Abstract

Digitalis drugs are selective inhibitors of the plasma membrane Na+/K+-ATPase. There are many studies on molecular mechanisms of digitalis interaction with purified pig kidney enzyme, with the tacit assumption that it is a good model of human kidney enzyme. However, previous studies on crude or recombinant human kidney enzymes are limited, and have not resulted in consistent findings on their digitalis sensitivities. Hence, we prepared comparably purified enzymes from human and pig kidneys and determined inhibitory constants of digoxin, ouabain, ouabagenin, bufalin, and marinobufagenin (MBG) on enzyme activity under optimal turnover conditions. We found that each compound had the same potency against the two enzymes, indicating that (i) the pig enzyme is an appropriate model of the human enzyme, and (ii) prior discrepant findings on human kidney enzymes were either due to structural differences between the natural and recombinant enzymes or because potencies were determined using binding constants of digitalis for enzymes under nonphysiological conditions. In conjunction with previous findings, our newly determined inhibitory constants of digitalis compounds for human kidney enzymes indicate that (i) of the compounds that have long been advocated to be endogenous hormones, only bufalin and MBG may act as such at kidney tubules, and (ii) beneficial effects of digoxin, the only digitalis with extensive clinical use, does not involve its inhibitory effect on renal tubular Na+/K+-ATPase.

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