Effects of sucralfate on gastric prostaglandin and leukotriene synthesis: relationship to protective actions.
The mechanism of the protective actions of sucralfate against ethanol-induced gastric mucosal damage in the rat has been investigated. In particular, the role of prostaglandins as mediators of such protection was assessed. Oral administration of sucralfate at a dose causing a significant reduction of ethanol-induced gastric damage (500 mg/kg) did not significantly alter gastric 6-ketoprostaglandin F1 alpha synthesis. Pretreatment with indomethacin at a dose that inhibited gastric cyclooxygenase activity by an average of 88% did not affect the protective actions of sucralfate. To further investigate the mechanism of action of sucralfate, an ex vivo gastric chamber model was used in which sucralfate could be applied to only one side of the mucosa. Sucralfate did not affect gastric prostaglandin synthesis, but did cause a significant increase in leukotriene C4 synthesis, a fall in transmucosal potential difference, and a significant decrease in gastric myeloperoxidase activity on the side exposed to sucralfate. These observations suggest that sucralfate has an irritant action on the mucosa. The release of mediators in response to such irritation may play an important role in the protective action of sucralfate. The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate.
Wallace
J L
JL
Department of Physiology, Queen's University, Kingston, Ont., Canada.
Morris
G P
GP
Beck
P L
PL
Williamson
T E
TE
Gingras
G R
GR
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D013270:Stomach / Q000187:drug effects*; D013392:Sucralfate / Q000494:pharmacology*
D011453:Prostaglandins; D013189:SRS-A; D000431:Ethanol; D013392:Sucralfate; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin