Effect of ranitidine bismuth citrate on the phospholipase A2 activity of Naja naja venom and Helicobacter pylori: a biochemical analysis.
BACKGROUND
Helicobacter pylori has become recognized as a fundamental pathogen in the development of gastritis and peptic ulcer disease. Bismuth compounds in combination with antibiotics are widely used to treat H. pylori associated peptic ulcer disease.


METHODS
In this study we measured and analysed the inhibitory effect of ranitidine bismuth citrate (RBC, Pylorid, Tritec) on the activity and kinetics of phospholipase A2 (PLA2) (E.C.3.1.1.4) of commercial cobra (Naja naja) venom and H. pylori (French press lysates) using L-alpha-dipalmitoyl-(2[1-14C]palmitoyl)-phosphatidylcholine as substrate.


RESULTS
Our data suggest that RBC might exert a dose-dependent uncompetitive inhibition on PLA2 activity of both H. pylori and Naja naja venom. the inhibitory effect of RBC on the PLA2 activity cannot be abolished by the optimal concentration of calcium (10 mM), indicating its mechanism to be unrelated to the displacement of calcium from the activation site of the enzyme.


CONCLUSIONS
Our results suggest that one of the mechanisms by which bismuth compounds are therapeutically effective in the treatment of H. pylori associated gastritis is by inhibiting the activity of the degradative PLA2 enzyme secreted by H. pylori. As a consequence of the inhibitory action of RBC on PLA2 of the bacteria, the extracellular and/or intracellular phospholipid components of the gastric mucosal barrier are preserved.
Ottlecz
A
A
Department of Integrative Biology, Pharmacology and Physiology, University of Texas, Medical School, Houston, Texas, USA.
Romero
J J
JJ
Lichtenberger
L M
LM
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001729:Bismuth / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000201:enzymology*; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010741:Phospholipases A / Q000187:drug effects*; D054467:Phospholipases A2; D011899:Ranitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D004546:Elapid Venoms; D006635:Histamine H2 Antagonists; C073340:ranitidine bismuth citrate; D011899:Ranitidine; D010741:Phospholipases A; D054467:Phospholipases A2; D001729:Bismuth