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Digestive Diseases and Sciences

, Volume 51, Issue 2, pp 274–281 | Cite as

Inhibition of Epidermal Growth Factor Receptor Activation Enhances In Vivo Histamine-Stimulated Gastric Acid Secretion in the Rat

  • Hanumantha R. Ancha
  • Hari B. Ancha
  • Dustin S. Tedesco
  • Angela R. Ward
  • Richard F. HartyEmail author
Esophageal, Gastric, and Duodenal Disorders

Abstract

Epidermal growth factor (EGF) and transforming growth factor α (TGFα) have been shown to inhibit gastric acid secretion through stimulation of the EGF receptor (EGFR). In this study we examined in vivo the effects of inhibition of the EGFR on histamine-stimulated acid secretion in the rat. Submaximal (1.5 mg/kg/hr) histamine-stimulated acid secretion was measured (μ Eq H+/2 hr) during infusion of EGFRtk inhibitors and ranitidine in anesthetized rats. EGFR phosphorylation in gastric mucosal tissue lysates was measured by Western blot analysis. Submaximal histamine-stimulated acid secretion was increased significantly by the EGFR inhibitors tyrphostin (Tyr) A46 and Tyr AG1478. Tyr A46 prevented TGFα (10 μ g/kg/hr)-mediated inhibition of maximal (5.0 μ g/kg/hr) histamine-stimulated acid output. Histamine caused a fourfold increase in EGFR phosphorylation which was inhibited by both Tyr and ranitidine. We conclude that the EGFRtk inhibitors, Tyr A46 and Tyr AG1478, significantly increased submaximal histamine-stimulated acid output and Tyr A46 prevented TGFα inhibition of histamine-stimulated acid secretion. These observations suggest that the EGFR is involved, in vivo, in the regulation of gastric acid secretion.

Key Words

gastric acid secretion epidermal growth factor receptor transforming growth factor α tyrphostin A46 tyrphostin AG1478 histamine rat 

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Hanumantha R. Ancha
    • 1
  • Hari B. Ancha
    • 1
  • Dustin S. Tedesco
    • 1
  • Angela R. Ward
    • 1
  • Richard F. Harty
    • 1
    • 2
    Email author
  1. 1.Section of Gastroenterology, Department of Internal MedicineUniversity of Oklahoma Health Sciences Center and Oklahoma City VA Medical CenterOklahoma CityUSA
  2. 2.Section of GastroenterologyOU Medical CenterOklahoma CityUSA

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