Indomethacin inhibition of hog gastric H+/K(+)-ATPase arises from its effect on both the enzyme protein and the lipid bilayer

J Biochem. 1994 Aug;116(2):250-6. doi: 10.1093/oxfordjournals.jbchem.a124515.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Cell Membrane / drug effects
  • Fluorescence
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / enzymology*
  • Gastric Mucosa / ultrastructure
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Hydrogen-Ion Concentration
  • Indomethacin / pharmacology*
  • Kinetics
  • Lipid Bilayers / metabolism*
  • Proton Pump Inhibitors*
  • Proton Pumps
  • Swine

Substances

  • Lipid Bilayers
  • Proton Pump Inhibitors
  • Proton Pumps
  • Adenosine Triphosphatases
  • H(+)-K(+)-Exchanging ATPase
  • Indomethacin