Mercury weakens membrane anchoring of Na-K-ATPase.
The presence of circulating inhibitors able to decrease the renal Na-K-adenosinetriphosphatase (ATPase) activity (natriuretic hormones) was postulated some 30 years ago. In the present work, the natriuretic inhibitor HgCl2 was selected as a model compound for the structural characterization of a possible natriuretic pathway for Na-K-ATPase modification. The structural effects of Na-K-ATPase inhibition by HgCl2 were assessed by trypsinolysis of the blocked enzyme in comparison with untreated preparations. The results show that inactivation of Na-K-ATPase by HgCl2 leads to the release of the alpha-subunit from the membrane preferentially in the E2 conformation but also in the E1 conformation. Apparently, HgCl2 weakens the membrane anchoring of the alpha-subunit, presumably by loosening the alpha-beta-subunit interaction. By this mechanism, the sensitivity of the Na-K-ATPase to extracellular drugs, hormones, and antibodies, as well as to intracellular proteases and other regulatory factors, could be altered.
Imesch
E
E
Department of Pharmacology, Geneva University Medical Center, Switzerland.
Moosmayer
M
M
Anner
B M
BM
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D008566:Membranes / Q000378:metabolism; D008628:Mercury / Q000494:pharmacology*; D008968:Molecular Conformation; D010539:Permeability; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014357:Trypsin / Q000494:pharmacology; D014494:Unithiol / Q000494:pharmacology
D014494:Unithiol; D014357:Trypsin; D000254:Sodium-Potassium-Exchanging ATPase; D008628:Mercury