Effect of omeprazole on eicosanoid formation in and release from guinea‐pig gastric mucosal cells

Abstract

1 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 PGF_1α), PGE₂, PGF_2α 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. 2 In all cell preparations PLA₂ activity was approximately 5 times higher than that of LAT. 3 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. 4 Gastric cells constantly produced PGI₂, PGE₂, PGF_2α and TXA₂. The main prostaglandins released were PGI₂ and PGE₂. PGF_2α and TXA₂ were released in smaller quantities. 5 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 μm. Only concentrations as high as 100 μm produced a significant reduction in PGE₂ release by 60%. No significant changes could be detected in the spontaneous release of PGF_2α and TXA₂. 6 Omeprazole dissolved in PEG pH 7 had no effect on PGI₂ release except at 100 μm which led to an insignificant decrease by 40%. 7 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.