Effect of omeprazole on eicosanoid formation in and release from guinea-pig gastric mucosal cells.
Guinea-pig gastric mucosal cells isolated by collagenase and pronase digestion were used to study the release of prostanoids prostaglandin I2 (PGI2; measured as 6-keto PGF1 alpha), PGE2, PGF2 alpha and thromboxane A2 (TXA2; measured as TXB2). Lysophosphatide acyltransferase (LAT) and phospholipase A2 (PLA2) were measured in the microsomal fraction of isolated but not separated gastric cells and isolated and enriched parietal and mucous cells. In all cell preparations PLA2 activity was approximately 5 times higher than that of LAT. Acid-activated omeprazole inhibited LAT in a concentration-dependent manner with similar IC50 values in gastric, parietal and mucous cells. It had no effect on PLA2. Gastric cells constantly produced PGI2, PGE2, PGF2 alpha and TXA2. The main prostaglandins released were PGI2 and PGE2. PGF2 alpha and TXA2 were released in smaller quantities. Omeprazole dissolved in polyethylene glycol 400 (PEG) pH 2 inhibited spontaneous PGI2 release in a concentration-dependent manner with an IC50 of 14.3 +/- 4.8 microM. Only concentrations as high as 100 microM produced a significant reduction in PGE2 release by 60%. No significant changes could be detected in the spontaneous release of PGF2 alpha and TXA2. Omeprazole dissolved in PEG pH 7 had no effect on PGI2 release except at 100 microM which led to an insignificant decrease by 40%. These data suggest that omeprazole beyond its inhibitory effect on parietal cell K+/H+-ATPase also affects gastric mucosal prostanoid formation and release. The inhibitory effect on PGI2 does not support the view that omeprazole protects the gastric mucosa by increasing prostanoid formation.
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D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002855:Chromatography, Thin Layer; D015232:Dinoprostone; D004537:Eicosanoic Acids / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008055:Lipids / Q000032:analysis; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000494:pharmacology; D013849:Thimerosal / Q000494:pharmacology
D004537:Eicosanoic Acids; D008055:Lipids; D011458:Prostaglandins E; D013849:Thimerosal; D011464:Epoprostenol; D000217:Acyltransferases; C031076:2-acylglycerophosphocholine acyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D009853:Omeprazole