Indomethacin inhibition of hog gastric H+/K(+)-ATPase arises from its effect on both the enzyme protein and the lipid bilayer.
Indomethacin showed a dose-, time-, and pH-dependent, noncompetitive inhibitory effect on hog gastric H+/K(+)-ATPase. Four percent of total indomethacin in the buffer (0.20 mmol/liter) bound to the H+/K(+)-ATPase vesicles (15 micrograms/ml). It markedly quenched the intrinsic fluorescence of the enzyme, and decreased the membrane fluidity. Thus, the inhibitor effect of indomethacin may arise from both a direct effect on the hydrolytic and H+ transport functions of the enzyme and a disturbing effect on the lipid bilayer of the vesicle.
Du
J
J
Department of Molecular Biology, Chinese Academy of Sciences, Beijing.
Li
S G
SG
Lin
Z H
ZH
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005453:Fluorescence; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D013552:Swine
D008051:Lipid Bilayers; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D007213:Indomethacin