Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclo-oxygenase, a key enzyme in prostaglandin production, is mainly in the constitutive form (COX-1) in gastric mucosa, whereas leucocytes have an inducible enzyme (COX-2). We report that indomethacin and its glycolic acid ester acemetacin have quantitatively different effects on prostanoid synthesis in these tissues. Human gastric mucosa (fresh operation specimens, cut finely and washed), and 1-1.5 x 10(6) human blood leucocytes stimulated with lipopolysaccharide (5 micrograms/ml), were incubated with acemetacin or indomethacin (0.1, 1, 10, 100 micrograms/ml). Eicosanoids in the medium were measured by radioimmunoassay (RIA). In leucocytes, acemetacin and indomethacin were more potent cyclo-oxygenase inhibitors than in the gastric mucosa, and both reduced the PGE levels to similar extents (70-98% and 72-100% respectively, n = 5). LTB4 was reduced only at 100 micrograms/ml of either drug. In gastric mucosal incubates, acemetacin was less potent than indomethacin in causing a concentration-related inhibition of PGE accumulation (19-74% vs 34-84%; n = 6, p < 0.05). Acemetacin was also less potent than indomethacin in reducing gastric 6-keto-PGF1 alpha and TXB2 (by 11-79% vs 45-72%, and 0-80% vs 29-80% respectively, p < 0.05). The finding that acemetacin is equipotent to indomethacin on leucocyte cyclo-oxygenase (inducible enzyme, COX-2) but less active on the gastric mucosa (COX-1) is consistent with an effective analgesic and anti-inflammatory activity of acemetacin coupled with better gastric tolerance than that to indomethacin.
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PMID:Acemetacin and indomethacin: differential inhibition of constitutive and inducible cyclo-oxygenases in human gastric mucosa and leucocytes. 814 13