Effects of gastrin on expression of cyclooxygenase and growth factors in rat gastric mucosa

AIM: To clarify the effects of gastrin on the expression of cyclooxygenase (COX) and several growth factors in rat gastric mucosa. METHODS: Male Sprague Dawley rats were fasted for 24 hours and subcutaneously injected with saline or gastrin 17 at doses of 1 μg/kg, 10 μg/kg and 100 μg/kg, respectively. The expression of COX-1, COX-2, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and hepatocyte growth factor (HGF) in the gastric mucosa were examined using Western blotting and immunohistochemical staining. Effects of a potent gastrin receptor antagonist YM022 on the expression of COX-1, COX-2, HB-EGF and HGF in gastric mucosa were also evaluated. RESULTS: Gastrin dose-dependently increased the expression of COX-2 and HB-EGF in rat gastric mucosa while the expression of COX-1 and HGF did not change significantly after treatment with gastrin. However, pretreatment with YM022 dose-dependently abolished the up-regulation of COX-2 and HB-EGF expression induced by gastrin. CONCLUSIONS: This study demonstrates that gastrin up-regulates COX-2 and HB-EGF expression in rat gastric mucosa, indicating that COX-2 and HB-EGF are involved in pathogenesis of the gastrin-related gastric mucosal hyperplasia and carcinoma of stomach.