Absence of an endogenous regulator of Na+,K+-ATPase activity in the tissues of cirrhotic rats.
Microsomal Na+,K+-ATPase isolated from the renal cortex of rats with CCL4-induced cirrhosis (CIR) showed a higher specific activity than the enzyme obtained from control rats (COR). Kinetic studies showed a lower K0.5 for ATP (0.08 +/- 0.03 vs. 0.24 +/- 0.04 mM; p less than 0.05), a lower Na+ activation constant (9.6 +/- 1.5 vs. 19.0 +/- 1.7 mM; p less than 0.05), and a higher K+ activation constant (1.2 +/- 0.1 vs. 0.6 +/- 0.1 mM; p less than 0.05) for CIR. The optimal pH of the enzyme was 0.5 units higher in CIR than COR. The fluorescence of eosin-treated enzymes indicated a higher ratio of E1/E2 forms of Na+,K+-ATPase in CIR. The K+-activated p-nitrophenylphosphatase (pNPPase) activity of the enzyme was lower in CIR than COR rats (1.5 +/- 0.1 vs. 2.2 +/- 0.1 mU/mg; p less than 0.05). Dialysing (24 h) COR microsomes reproduced most of the changes observed in CIR enzymes (kinetics, optimal pH, and eosin fluorescence). Lyophilized dialysate of COR, but not of CIR microsomes, inhibits Na+,K+-ATPase activity. These results suggest that a dialysable inhibitor modifies the Na+,K+-ATPase activity in the kidney of COR which is almost absent in that of CIR. The absence of this factor may lead to the overall inability to excrete Na+ in the cirrhotic state.
Tejedor
A
A
Department of Nephrology, Fundacion Jimenez Diaz, Madrid, Spain.
Conesa
D
D
Hernando
N
N
Hernando
L
L
Lopez-Novoa
J M
JM
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D003956:Dialysis; D004910:Erythrocyte Membrane / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010042:Ouabain / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D010710:Phosphates; D010042:Ouabain; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase