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), transform ing 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 protect ive activity of EGF, TGFalpha and bFGF against mucosal damage and the expression of the growth factor receptors in rat gastric mucosa were a ssessed. Acute mucosal lesions were induced by intragastric applicatio n of absolute ethanol, acidified aspirin or water immersion and restra int stress. Results: Specific binding of labeled growth factor to cyto plasmic membranes prepared from rat gastric mucosa revealed a relative ly high density of receptors for EGF and TGFalpha (2.46-3.45 fmol/mg p rotein), while the binding capacity of bFGF was significantly lower (0 .62 fmol/mg protein). EGF or TGFalpha, infused subcutaneously (12.5-10 0 mug/kg/h), dose-dependently reduced gastric acid and pepsin secretio n, increased gastric blood flow and prevented acute mucosal damage ind uced by all three ulcerogens. By contrast, bFGF (12.5-100 mug/kg/h) in hibited damage induced by water immersion and restraint stress, but no t that caused by acidified aspirin or ethanol. Suppression of prostagl andin generation by intraperitoneal indomethacin (5 mg/kg) partly reve rsed the protective effect of EGF and TGFalpha against ethanol, and co mpletely abolished the protective and hyperemic activities of all thre e growth factors in those rats exposed to water immersion and restrain t stress. Conclusions: TGFalpha and EGF, but not bFGF, protect the sto mach against drug-induced acute mucosal damage, while all three protec t against stress-induced lesions. The acute protection afforded by the se growth factors appears to depend, in part, on preservation of the m ucosal microcirculation.