Inhibition of gastric H+,K(+)-ATPase by the anti-ulcer agent, sofalcone.

Effects of the anti-ulcer agent, sofalcone, on gastric H+,K(+)-ATPase were studied as well as those of other chalcone derivatives, chalcone and sophoradin. These drugs inhibited pig gastric H+,K(+)-ATPase in a dose-dependent manner. They were 5-10-fold less inhibitory toward Na+,K(+)-ATPase than H+,K(+)-ATPase. The potencies of these drugs on the inhibition of enzymes were as follows: sophoradin greater than sofalcone greater than chalcone. Kinetic studies showed that the inhibition of H+,K(+)-ATPase by sofalcone was competitive with respect to ATP and was non-competitive with respect to K+. Sofalcone also inhibited H+,K(+)-ATPase mediated proton transport and reduced the phosphoenzyme level. These results suggest that sofalcone inhibits gastric H+,K(+)-ATPase competitively with ATP at the ATP site and thereby blocks the phosphorylation of the enzyme. This may be the cause of the anti-secretory activity of sofalcone.