PMID- 12190125 OWN - NLM STAT- MEDLINE DCOM- 20030410 LR - 20220311 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 236 IP - 1-2 DP - 2002 Jul TI - Comparison of the antisecretory and antiulcer activity of epidermal growth factor, urogastrone and transforming growth factor alpha and its derivative in rodents in vivo. PG - 83-94 AB - 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. FAU - Bastaki, S M A AU - Bastaki SM AD - Department of Pharmacology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain. sbastaki@uaeu.ac.ae FAU - Chandranath, S I AU - Chandranath SI FAU - Singh, J AU - Singh J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Prostaglandins) RN - 0 (Transforming Growth Factor alpha) RN - 62229-50-9 (Epidermal Growth Factor) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.13 (Protein Kinase C) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) RN - XXE1CET956 (Indomethacin) SB - IM MH - Animals MH - Cyclic AMP/metabolism MH - Dose-Response Relationship, Drug MH - Epidermal Growth Factor/*metabolism/*physiology MH - Female MH - Gastric Acid/metabolism MH - Indomethacin/pharmacology MH - Male MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Prostaglandins/metabolism MH - Protein Kinase C/metabolism MH - Protein Structure, Tertiary MH - Rats MH - Rats, Wistar MH - Signal Transduction MH - Time Factors MH - Transforming Growth Factor alpha/*metabolism EDAT- 2002/08/23 10:00 MHDA- 2003/04/11 05:00 CRDT- 2002/08/23 10:00 PHST- 2002/08/23 10:00 [pubmed] PHST- 2003/04/11 05:00 [medline] PHST- 2002/08/23 10:00 [entrez] AID - 10.1023/a:1016144016908 [doi] PST - ppublish SO - Mol Cell Biochem. 2002 Jul;236(1-2):83-94. doi: 10.1023/a:1016144016908.