Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells

• Published in: European journal of pharmacology 1998-04, Vol.347 (1), p.87-94
• Main Authors: Kawai, Shinichi, Nishida, Shinichi, Kato, Miyako, Furumaya, Yasuko, Okamoto, Renzo, Koshino, Tomihisa, Mizushima, Yutaka
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - enzymology; Blood Platelets - metabolism; Blotting, Western; Bones, joints and connective tissue. Antiinflammatory agents; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Cytokines - pharmacology; Dinoprostone - biosynthesis; Humans; Isoenzymes - blood; Isoenzymes - drug effects; Isoenzymes - metabolism; Medical sciences; Membrane Proteins; Nonsteroidal anti-inflammatory drug; Pharmacology. Drug treatments; Platelet; Polymerase Chain Reaction; Precipitin Tests; Prostaglandin-Endoperoxide Synthases - blood; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Synovial cell; Synovial Membrane - drug effects; Synovial Membrane - enzymology; Synovial Membrane - metabolism; Transcription, Genetic
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00078-8

Recent studies have shown that cyclooxygenase exists in two isozyme forms. Since differences in the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) might be accounted for by varying degrees of selectivity for these isozymes, cyclooxygenase-1 and -2, the relative potency of various NSAIDs in inhibiting their activities was examined in intact human cells. We used human platelets cyclooxygenase-1 and interleukin-1 β-stimulated human synovial cell cyclooxygenase-2 for measuring cyclooxygenase selectivity. The presence of the enzymes was confirmed by immunoblotting and immunoprecipitation analysis, and by the reverse transcriptase-polymerase chain reaction. Mean IC 50 values ( μM) for human platelet cyclooxygenase-1 and interleukin-1 β-stimulated human synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC 50 ratio of various NSAIDs were as follows: aspirin, 3.2, 26, 0.12; diclofenac, 0.037, 0.00097, 38; etodolac, 122, 0.68, 179; ibuprofen, 3.0, 3.5, 0.86; indomethacin, 0.013, 0.044, 0.30; loxoprofen (active metabolite), 0.38, 0.12, 3.2; NS-398, 12, 0.0095, 1263; oxaprozin, 2.2, 36, 0.061; zaltoprofen, 1.3, 0.34, 3.8; respectively. Our bioassay system employing intact human cells to assess the cyclooxygenase selectivity of NSAIDs may provide clinically useful information.