[Effect of indomethacin on H+ transportation of pig gastric H+/K(+)-ATPase].
As a noncompetitive inhibitor of pig gastric H+/K(+)-ATPase, indomethacin inhibited the H+ transportation function of the enzyme, leading to not only the obvious dissipation of H+/K(+)-ATPase-generated H+ gradients, but also the decreasing of the H+ gradient formation ability of the enzyme. 4% of indomethacin was able to penetrate into the lipid bilayer of H+/K(+)-ATPase vesicles at 0.15 mg/ml protein concentration, which showed an influence of indomethacin to the membrane. Indomethacin reduced the membrane fluidity of H+/K(+)-ATPase vesicles significantly. It also damaged the conformation of membrane protein extraordinarily, which was evidenced by decreasing the intrinsic fluorescence of H+/K(+)-ATPase. From the results, we suggest that the effect of indomethacin on H+/K(+)-ATPase is taken place by its inhibition on H+/K(+)-ATPase protein, as well as by its influence on the membrane lipid bilayer of H+/K(+)-ATPase vesicles.
Du
J
J
Division of Biomembrane, Chinese Academy of Science, Beijing.
Lin
Z H
ZH
Li
S G
SG
D000818:Animals; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D008051:Lipid Bilayers; D008560:Membrane Fluidity / Q000187:drug effects; D011522:Protons; D013270:Stomach / Q000201:enzymology*; D013552:Swine
D008051:Lipid Bilayers; D011522:Protons; D017506:H(+)-K(+)-Exchanging ATPase; D007213:Indomethacin