Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells.
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-1beta-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 IC50 values (microM) for human platelet cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC50 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.
Kawai
S
S
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan. s2kawai@marianna-u.ac.jp
Nishida
S
S
Kato
M
M
Furumaya
Y
Y
Okamoto
R
R
Koshino
T
T
Mizushima
Y
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D014158:Transcription, Genetic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone