LY 186655，一种磷酸二酯酶抑制剂，可抑制人嗜碱性粒细胞、肺和皮肤碎片释放组胺。

LY 186655, a phosphodiesterase inhibitor, inhibits histamine release from human basophils, lung and skin fragments.

作者信息

Louis R, Bury T, Corhay J L, Radermecker M

机构信息

Department of Respiratory Medicine, C.H.U. Sart Tilman, University of Liège, Belgium.

出版信息

Int J Immunopharmacol. 1992 Feb;14(2):191-4. doi: 10.1016/0192-0561(92)90030-o.

DOI:10.1016/0192-0561(92)90030-o

PMID:1378045

Abstract

LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived from the xanthine, possessing bronchodilating activity in animals. The aim of this work was to study the effect of LY 186655 and theophylline on histamine release from human leukocytes, skin and lung fragments. Histamine was measured using a spectrofluorometric method. Both drugs (3 x 10(-5)-3 x 10(-3) M) exhibited a dose-dependent inhibition on anti-IgE (1/2000)-induced histamine release from human leukocytes. At 3 x 10(-3) M, theophylline was significantly more effective than LY 186655 (mean inhibition 94 and 42%, respectively). On lung fragments, theophylline and LY 186655 (3 x 10(-5)-3 x 10(-3) M) caused strong and comparable inhibitory effects on anti-IgE (1/500)-induced histamine release with a mean inhibition reaching maximally 65%. Histamine release induced by compound 48/80 (1 mg/ml) on sliced human foreskin was reduced with both drugs (3 x 10(-3) M) by about 37%. We conclude that LY 186655 inhibits in vitro immunological histamine release from human lung and cutaneous mast cells as well as basophils with a similar pattern of activity to theophylline.

摘要

LY 186655（替贝司特，礼来公司）是一种新型磷酸二酯酶抑制剂，并非源自黄嘌呤，在动物体内具有支气管扩张活性。本研究的目的是探讨LY 186655和茶碱对人白细胞、皮肤及肺组织碎片中组胺释放的影响。采用荧光分光光度法测定组胺含量。两种药物（3×10⁻⁵ - 3×10⁻³ M）均对抗IgE（1/2000）诱导的人白细胞组胺释放呈现剂量依赖性抑制作用。在3×10⁻³ M时，茶碱的效果显著优于LY 186655（平均抑制率分别为94%和42%）。在肺组织碎片上，茶碱和LY 186655（3×10⁻⁵ - 3×10⁻³ M）对抗IgE（1/500）诱导的组胺释放产生强烈且相当的抑制作用，平均抑制率最高可达65%。两种药物（3×10⁻³ M）均可使化合物48/80（1 mg/ml）诱导的人包皮切片组胺释放减少约37%。我们得出结论，LY 186655在体外可抑制人肺和皮肤肥大细胞以及嗜碱性粒细胞的免疫性组胺释放，其活性模式与茶碱相似。