Gastric mucosal cell protection by epidermal growth factor in primary monolayer culture of guinea pig gastric mucous cells.
BACKGROUND
Epidermal growth factor (EGF) has an anti-ulcer effect, but the mechanisms of this gastric mucosal protection are incompletely understood. We have suggested the importance of mucin as a mucosal protectant. We investigated whether increased mucin biosynthesis might be involved in the gastric mucosal protection conferred by EGF.


METHODS
EGF and then ethanol were added to primary monolayer cultures of guinea pig gastric mucous cells, in which factors such as gastric acid and gastrointestinal hormones were excluded. Mucin and prostaglandin E(2) (PGE(2)) were assayed.


RESULTS
Cytoprotection induced by EGF was demonstrated. Mucin biosynthesis and PGE(2) release were both significantly increased by EGF. When endogenous PGE(2) synthesis was inhibited by pretreatment with 10(-5) M or 10(-4) M indomethacin (IND), mucin biosynthesis was still significantly increased by EGF. Ethanol-induced cell damage was concentration-dependent in cultures with no other additions (normal PGE(2) and mucin biosynthesis). Damage by ethanol was decreased by EGF pretreatment (increased PGE(2) and mucin biosynthesis). Damage by ethanol was increased by 10(-5) M IND pretreatment (decreased PGE(2); normal mucin biosynthesis) and by 10(-4) M IND pretreatment (decreased PGE(2) and mucin biosynthesis). Ethanol-induced damage was decreased by EGF pretreatment even in the presence of 10(-5) M and 10(-4) M IND (decreased PGE(2); increased mucin biosynthesis).


CONCLUSIONS
Increased mucin biosynthesis, induced by EGF independently of PGE(2), protects gastric mucous cells.
D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005752:Gastric Mucins / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male
D005752:Gastric Mucins; D000431:Ethanol; D004815:Epidermal Growth Factor; D015232:Dinoprostone