Yoneta T, Kato H, Yoshida A, Ozeki M, Tagashira E
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Nihon Yakurigaku Zasshi. 1991 Jan;97(1):23-30. doi: 10.1254/fpj.97.1_23.
We studied the effects of CN-100 on the functions of rat polymorphonuclear leukocytes (PMN) in vitro. CN-100 showed the inhibitory effects of superoxide production and luminol dependent chemiluminescence induced by opsonized zymosan (OZ) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) in PMN, and its inhibitory activity was almost equipotent to that of indomethacin and more than that of pranoprofen. Preincubation of cytochalasin E-treated PMN with CN-100, indomethacin and pranoprofen resulted in dose-dependent inhibition of lysosomal enzyme release elicited by OZ or FMLP, but pranoprofen was less potent than CN-100 and indomethacin. CN-100 and indomethacin inhibited the increase of intracellular calcium in FuraII loaded PMN stimulated by FMLP. The inhibitions by both agents were reversible. These findings indicated that the reversible interaction between CN-100 and PMN membrane inhibit signal transduction starting from intracellular calcium mobilization in PMN and suppress many PMN's functions. These results suggest that CN-100 has an inhibitory activity on PMN function which is as potent as that of indomethacin.
我们在体外研究了CN - 100对大鼠多形核白细胞(PMN)功能的影响。CN - 100对PMN中由调理酵母聚糖(OZ)或N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸(FMLP)诱导的超氧化物生成和鲁米诺依赖性化学发光具有抑制作用,其抑制活性几乎与吲哚美辛相当,且强于普拉洛芬。用细胞松弛素E处理过的PMN预先与CN - 100、吲哚美辛和普拉洛芬孵育,会导致由OZ或FMLP引发的溶酶体酶释放呈剂量依赖性抑制,但普拉洛芬的效力低于CN - 100和吲哚美辛。CN - 100和吲哚美辛抑制了FMLP刺激的负载FuraII的PMN中细胞内钙的增加。两种药物的抑制作用都是可逆的。这些发现表明,CN - 100与PMN膜之间的可逆相互作用抑制了从PMN细胞内钙动员开始的信号转导,并抑制了许多PMN的功能。这些结果表明,CN - 100对PMN功能具有与吲哚美辛相当的抑制活性。