Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti-inflammatory agents

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Abstract
1 Homogenates of rat gastric mucosa, forestomach and ileum and dog gastric mucosa reproducibly generated prostacyclin from endogenous substrate. 2 Prostacyclin formation was inhibited by pre-incubation with indomethacin, flurbiprofen, naproxen, ketoprofen or meclofenamate (0.1–10 μm). 3 BW755C (3-amino-1[m-(trifluoromethyl)-phenyl]-2-pyrazoline) stimulated prostacyclin production in the rat gastric mucosa and ileum with inhibition occurring only at high concentrations (>200 μm). The stimulation of prostacyclin production by BW755C in rat forestomach homogenates was less pronounced, with inhibition at concentrations > 20 μm. 4 BW755C thus exhibits differential activity on prostacyclin production from different gastric tissues in vitro. 5 The antioxidant-lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA, 3–15 μm) likewise augmented rat mucosal prostacyclin formation. 6 Paracetamol stimulated and, at higher concentrations, inhibited prostacyclin formation (> 1 mm), and had comparable activity in both rat gastric tissues. 7 The ability of NDGA and BW755C to enhance prostacyclin generation may reflect the removal of a modulating influence of lipoxygenase products on prostacyclin formation, the diversion of substrate to the cyclo-oxygenase pathway, or free-radical scavenging.

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