Kawai S, Nishida S, Kato M, Furumaya Y, Okamoto R, Koshino T, Mizushima Y
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Eur J Pharmacol. 1998 Apr 17;347(1):87-94. 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-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.
近期研究表明，环氧化酶以两种同工酶形式存在。由于非甾体抗炎药（NSAIDs）药理特性的差异可能是由对这些同工酶（环氧化酶-1和-2）不同程度的选择性所致，因此在完整的人类细胞中检测了各种NSAIDs抑制其活性的相对效力。我们用人血小板环氧化酶-1和白细胞介素-1β刺激的人滑膜细胞环氧化酶-2来测定环氧化酶选择性。通过免疫印迹、免疫沉淀分析以及逆转录酶-聚合酶链反应证实了酶的存在。各种NSAIDs对人血小板环氧化酶-1和白细胞介素-1β刺激的人滑膜细胞环氧化酶-2的平均IC50值（微摩尔）以及环氧化酶-1/-2的IC50比值如下：阿司匹林，3.2、26、0.12；双氯芬酸，0.037、0.00097、38；依托度酸，122、0.68、179；布洛芬，3.0、3.5、0.86；吲哚美辛，0.013、0.044、0.30；洛索洛芬（活性代谢物），0.38、0.12、3.2；NS-398，12、0.0095、1263；奥沙普秦，2.2、36、0.
