Bismuth subcitrate and omeprazole inhibit Helicobacter pyloriF1-ATPase.
The effects of various types of antiulcer agents against Helicobacter pylori F1-ATPase were studied. ATPase was released into the aqueous phase (i.e., solubilized) by sonication. The enzyme activity depended on Mg2+, but not Ca2+. The maximum activity occurred at an ATP/Mg2+ ratio of 1/5 and at pH 7.5. Mg(2+)-dependent ATPase activity was inhibited by sodium azide and the monovalent cations K+ and Na+, but not by oligomycin, dicyclohexylcarbodiimide, ouabain, or SCH 28080. The antiulcer agents ranitidine, pirenzepine, aluminum hydroxide, and sucralfate failed to influence H. pylori F1-ATPase. In contrast, bismuth subcitrate and the H+/K(+)-ATPase inhibitor omeprazole inhibited the enzyme. Inhibition was prevented and reversed by the mercaptan glutathione, indicating that both drugs interfere with sulfhydryl groups of the enzyme. The data suggest that bismuth subcitrate and omeprazole owe their antibacterial activity against H. pylori, at least in part, to inhibition of F1-ATPase, an enzyme involved in bacterial energy metabolism.
Beil
W
W
Department of General Pharmacology, Medizinische Hochschule Hannover, Germany.
Birkholz
C
C
Wagner
S
S
Sewing
K F
KF
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology*; D009853:Omeprazole / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D012995:Solubility
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D006180:Proton-Translocating ATPases; C002791:bismuth tripotassium dicitrate; D009853:Omeprazole