Increased hepatocyte growth factor content in rat stomach during omeprazole treatment

Digestion. 1998;59(2):102-9. doi: 10.1159/000007474.

Abstract

Background and aims: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing.

Methods: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested.

Results: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice.

Conclusion: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Gastric Acid / chemistry
  • Gastric Acidity Determination
  • Gastric Juice / chemistry
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastrointestinal Agents / chemistry
  • Gastrointestinal Agents / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation / drug effects
  • Genes / genetics
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Hepatocyte Growth Factor / pharmacology
  • Hydrogen-Ion Concentration / drug effects
  • Hydrolysis / drug effects
  • Indomethacin / administration & dosage
  • Indomethacin / adverse effects
  • Indomethacin / pharmacology
  • Male
  • Omeprazole / administration & dosage
  • Omeprazole / pharmacology*
  • Pepsin A / chemistry
  • Pepsin A / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stomach / chemistry
  • Stomach / drug effects*
  • Stomach Diseases / chemically induced
  • Stomach Diseases / drug therapy
  • Wound Healing / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Gastrointestinal Agents
  • Hepatocyte Growth Factor
  • Pepsin A
  • Omeprazole
  • Indomethacin