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选择性磷酸二酯酶4(PDE4)抑制剂对豚鼠皮肤嗜酸性粒细胞募集的抑制活性比较。

A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin.

作者信息

Teixeira M M, Miotla J M, Cooper N, Gristwood R W, Hellewell P G

机构信息

Imperial College of Medicine, National Heart and Lung Institute, London, UK.

出版信息

Mem Inst Oswaldo Cruz. 1997;92 Suppl 2:193-6. doi: 10.1590/s0074-02761997000800025.

Abstract

The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibit eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo.

摘要

磷酸二酯酶(PDE)4抑制剂使嗜酸性粒细胞内的环磷酸腺苷(cAMP)升高,这与抑制这些细胞的活化和募集有关。我们之前已经表明,用PDE4抑制剂咯利普兰进行全身治疗可有效抑制豚鼠皮肤中嗜酸性粒细胞的迁移。在本研究中,我们比较了PDE4抑制剂咯利普兰、RP 73401和CDP 840对变应性和血小板活化因子(PAF)诱导的嗜酸性粒细胞募集的口服效力和疗效。咯利普兰和RP 73401经口服给药时同样有效且效力强大,比PDE4抑制剂CDP 840活性高得多。我们认为,这种变应性和介质诱导的嗜酸性粒细胞募集的豚鼠模型是一种在体内测试PDE4抑制剂疗效和效力的灵敏且简单的工具。

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