Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti-inflammatory agents.
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 muM).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 muM). The stimulation of prostacyclin production by BW755C in rat forestomach homogenates was less pronounced, with inhibition at concentrations > 20 muM.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 muM) 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.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009637:Masoprocol; D011453:Prostaglandins / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D002396:Catechols; D011453:Prostaglandins; D011720:Pyrazoles; D000082:Acetaminophen; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D011464:Epoprostenol