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.
Murakami
S
S
Research Center, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
Muramatsu
M
M
Aihara
H
H
Otomo
S
S
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D017506:H(+)-K(+)-Exchanging ATPase; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011522:Protons; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine
D000814:Aniline Compounds; D000897:Anti-Ulcer Agents; D047188:Chalcones; D009943:Organophosphorus Compounds; D011522:Protons; C035032:sofalcone; D002599:Chalcone; C068798:4-aminophenylphosphate; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase