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

Abstract

Homogenates of rat gastric mucosa, forestomach and ileum and dog gastric mucosa reproducibly generated prostacyclin from endogenous substrate. Prostacyclin formation was inhibited by pre‐incubation with indomethacin, flurbiprofen, naproxen, ketoprofen or meclofenamate (0.1–10 μm). 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. BW755C thus exhibits differential activity on prostacyclin production from different gastric tissues in vitro. The antioxidant‐lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA, 3–15 μm) likewise augmented rat mucosal prostacyclin formation. Paracetamol stimulated and, at higher concentrations, inhibited prostacyclin formation (> 1 mm), and had comparable activity in both rat gastric tissues. 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.

Differential Effect of Benexate Hydrochloride Betadex on Prostaglandin Levels in Stomach and Inflammatory Site in Rats

“…In the present study, the normal endogenous levels of PGs (PGE2 was around 1 ng/g tissue and 6-keto-PGFicr, around 3 ng/g tissue) were similar to those reported by Suzuki et al (12), but much lower than those (50-100 ng/g tissue) in other studies (14,15), the latter probably reflecting the artifact generation of PGs due to the chopping and scraping of gastric mucosa. The strong and sustained decrease of gastric PGs, particularly PGE2 by the lesion-inducing dose of indomethacin, is consistent with already documented results (16,17), and we also confirmed significant recovery by BHB of the indomethacin-induced decrease of gastric PGs with doses capable of inhibiting indomethacin-induced gastric mucosal lesion (5).…”

The Intestinal Microvasculature as a Therapeutic Target in Inflammatory Bowel Disease

“…[82][83][84] In human IBD, thromboxane production in cultured isolated intestinal epithelial cells from patients with ulcerative colitis and those with Crohn's disease is increased. 85,86 In addition, in active colonic tissue homogenates from patients with ulcerative colitis 87,88 and in cultured biopsies from patients with both ulcerative colitis or Crohn's disease, excess thromboxane production is observed. [89][90][91] Moreover, rectal dialysis in patients with ulcerative colitis and Crohn's disease shows increased rectal mucosal production of thromboxane in active disease in vivo.…”

Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease

“…Within human IBD, thromboxane production in cultured isolated intestinal epithelial cells from patients with UC and those with CD is increased [115,116]. Additionally, in active colonic tissue homogenates from patients with UC [117,118] and in cultured biopsies from both patients with UC or CD excess thromboxane production was observed [119–121]. Moreover, rectal dialysis in patients with UC and CD showed increased rectal mucosal production of thromboxane in active disease in vivo [122–125].…”