GASTROPROTECTIVE ACTIVITY AND RECEPTOR EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA, EPIDERMAL GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR IN THE RAT STOMACH

Objective: To assess receptor expression in the gastric mucosa and the gastroprotective activity of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and basic fibroblast growth factor (bFGF), three potent mitogens which are known to stimulate the healing of a variety of wounds including chronic ulcers. Methods: The protective activity of EGF, TGFalpha and bFGF against mucosal damage and the expression of the growth factor receptors in rat gastric mucosa were assessed. Acute mucosal lesions were induced by intragastric application of absolute ethanol, acidified aspirin or water immersion and restraint stress. Results: Specific binding of labeled growth factor to cytoplasmic membranes prepared from rat gastric mucosa revealed a relatively high density of receptors for EGF and TGFalpha (2.46-3.45 fmol/mg protein), while the binding capacity of bFGF was significantly lower (0.62 fmol/mg protein). EGF or TGFalpha, infused subcutaneously (12.5-100 mug/kg/h), dose-dependently reduced gastric acid and pepsin secretion, increased gastric blood flow and prevented acute mucosal damage induced by all three ulcerogens. By contrast, bFGF (12.5-100 mug/kg/h) inhibited damage induced by water immersion and restraint stress, but not that caused by acidified aspirin or ethanol. Suppression of prostaglandin generation by intraperitoneal indomethacin (5 mg/kg) partly reversed the protective effect of EGF and TGFalpha against ethanol, and completely abolished the protective and hyperemic activities of all three growth factors in those rats exposed to water immersion and restraint stress. Conclusions: TGFalpha and EGF, but not bFGF, protect the stomach against drug-induced acute mucosal damage, while all three protect against stress-induced lesions. The acute protection afforded by these growth factors appears to depend, in part, on preservation of the mucosal microcirculation.