Inhibition of epidermal growth factor receptor activation enhances in vivo histamine-stimulated gastric acid secretion in the rat

Epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) 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. S...

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Published in:Digestive diseases and sciences 2006-02, Vol.51 (2), p.274-281
Main Authors: ANCHA, Hanumantha R, ANCHA, Hari B, TEDESCO, Dustin S, WARD, Angela R, HARTY, Richard F
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Gastric Acid - secretion
Histamine
Histamine H2 Antagonists - pharmacology
Male
Phosphorylation - drug effects
Quinazolines
Ranitidine - pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - physiology
Transforming Growth Factor alpha - physiology
Tyrphostins - pharmacology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) 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 (microEq 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 TGFalpha (10 microg/kg/hr)-mediated inhibition of maximal (5.0 microg/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 TGFalpha inhibition of histamine-stimulated acid secretion. These observations suggest that the EGFR is involved, in vivo, in the regulation of gastric acid secretion.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-006-3125-z