title: Phospholipase inhibition and prostacyclin generation by gastric muscularis and mucosa layers.
abstract: The effects of drugs which interfere with arachidonate metabolism as well as glucocorticoid-induced anti-phospholipase proteins (APP) have been studied on PGI2 generation by rat stomach tissue. Indomethacin inhibited PGI2 generation both in vitro and ex vivo while dexamethasone was ineffective in both instances. APP inhibited PGI2 generation in vitro. The results are discussed in the light of the possible mode of action of glucocorticoids. Prostacyclin (PGI2) is the major cyclo oxygenase metabolite in the rat gastric mucosa and exerts gastroprotective actions. Therefore a correlation between the inhibition of PGI2 synthesis and the induction of gastric damage has been suggested for the non-steroidal anti-inflammatory drugs. Glucocorticoids inhibit phospholipase A2 (PLA2) by inducing in the target cells the synthesis of inhibitory proteins, the lipocortins, and consequently reduce the release of eicosanoids in a number of cells and tissues. However, there is a surprising paucity of information on the effect of glucocorticoids on arachidonic acid (AA) metabolism in the gastro-intestinal tract. Moreover, the relationship between steroid administration and gastric damage is still controversial. The present work was undertaken to investigate the effect of drugs which interfere with AA metabolism on the synthesis of PGI2 by rat stomach mucosa and by the underlying muscularis layer both in vitro and ex vivo.
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects
chemical_list: D003907:Dexamethasone; D011464:Epoprostenol; D010740:Phospholipases; D007213:Indomethacin