This study investigates the effects of
epidermal growth factor (
EGF),
urogastrone (UG) and
transforming growth factor-alpha (
TGFalpha) and its derivative on
dimaprit- and
pentagastrin-induced gastric acid secretion and on acidified
ethanol (AE)-evoked
ulcer formation in anaesthetized rats.
EGF,
TGFalpha and UG administered subcutaneously (s.c.) 30 min before
dimaprit inhibited gastric acid secretion. Against
pentagastrin-stimulated secretion,
TGFalpha inhibited, while
EGF and UG potentiated,
acid secretion dose-dependently. Intraduodenal (i.d.) administration of
TGFalpha and UG had no effect, while
EGF potentiated, both
secretagogue-induced
acid secretion in the same dosage schedule. Administration of either
EGF, UG or
TGFalpha i.v. bolus, in response to continuous infusion of
dimaprit resulted in a significant (p < 0.05-p < 0.001) inhibition of
acid secretion which was transient and returned to normal within 30-45 min for UG while it slowly returned to normal for
EGF and
TGFalpha. The truncated form of TGFa (
amino acids 34-43) did not show any antisecretory effect when administered parenterally. Acidified
ethanol produced gastric haemorrhagic lesions in the rat 1 h after
oral administration. The gastric mucosal protective effects of
TGFalpha,
EGF and UG administered either orally or s.c. 30 min before the administration of AE were dose-dependent against this model of
ulcer induction.
Indomethacin (Indo), administered 15 min before AE to inhibit
prostanoids biosynthesis, significantly (p < 0.001) reduced the cytoprotective effects of
TGFalpha,
EGF and UG and aggravated the
ulcer index when administered s.c. The results show that PGs may be involved in mediating the protective effects of the three
growth factors. Administration of NG-nitro-L argininemethylester (
L-NAME) 15 min prior to TGFa,
EGF and UG s.c. or orally, significantly (p < 0.001) decreased the degree of
ulcer indices and was able to reduce the protective effects of
TGFalpha,
EGF and UG, thus including the role of NO in mediating the protective effects of these
growth factors. In conclusion, these results have demonstrated that
EGF, UG and
TGFalpha have a short and reversible inhibitory effect on
dimaprit-stimulated gastric acid secretion and each is effective parenterally but not orally. UG and
EGF potentiated, while, TGFa inhibited
pentagastrin-stimulated
acid secretion. In addition,
TGFalpha seems to lose its activity when it is truncated from the C terminus. The present study also suggests that
EGF, UG and
TGFalpha are equally effective against AE-induced
gastric ulcer and bring about their cytoprotective action through their reduction of
acid secretion and through PG and NO pathways.