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 i nhibitory effect on hog gastric H+/K+-ATPase. Four percent of total in domethacin in the buffer (0.20 mmol/liter) bound to the H+/K+-ATPase v esicles (15 mu g/ml). It markedly quenched the intrinsic fluorescence of the enzyme, and decreased the membrane fluidity. Thus, the inhibito r effect of indomethacin may arise from both a direct effect on the hy drolytic and H+ transport functions of the enzyme and a disturbing eff ect on the lipid bilayer of the vesicle.