Cytoprotective effect of epidermal growth factor on acid- and pepsin-induced damage to rat gastric epithelial cells: roles of Na+/H+ exchangers.
We have previously established a cell damage model, with damage induced by either acid or pepsin treatment for 30 min, involving a rat gastric epithelial cell line (RGM1). In the present study, pretreatment of cells with epidermal growth factor (EGF; 0.1-10 ng/mL) or sucralfate (0.1-3 mg/mL) for 4 h prevented such cell damage in a concentration-dependent manner. Protection of cells by these drugs was not affected by pretreatment with indomethacin (10(-5) mol/L) for 4 h. Removal of Na+, but not Ca2+, from the acidified medium totally abolished the inhibitory effect of EGF, but not that of sucralfate. Genistein (a tyrosine kinase inhibitor) apparently reduced the inhibitory effect of EGF. DNA synthesis by RGM1 cells did not increase when cells were incubated with EGF for 4 h. We conclude that both EGF and sucralfate protect RGM1 cells from acid- and pepsin-induced damage and that the mechanism of protection by EGF against acid-induced damage seems to be via activation of Na+/H+ exchangers.
Furukawa
O
O
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okabe
S
S
D000143:Acids / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology; D019833:Genistein; D006131:Growth Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D010434:Pepsin A / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D013392:Sucralfate / Q000494:pharmacology
D000143:Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D005765:Gastrointestinal Agents; D006131:Growth Inhibitors; D007529:Isoflavones; D017923:Sodium-Hydrogen Exchangers; D013392:Sucralfate; D004815:Epidermal Growth Factor; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010434:Pepsin A; D007213:Indomethacin