SK&F 96365年,一种新型抑制剂的受体介导钙条目。

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梅里特我,阿姆斯特朗WP,班CD,哈勒姆TJ,雅各R, Jaxa-Chamiec, Leigh BK麦卡锡SA摩尔KE,溜冰场TJ

SK&F 96365年,一种新型抑制剂的受体介导钙条目。

j . 1990 10月15日,271(2):515 - 22所示。doi: 10.1042 / bj2710515。

PubMed ID

2173565 (在PubMed

]

文摘

一种新型抑制剂的受体介导钙条目(RMCE)。SK&F 96365(1 -(β- [3 - (4-methoxy-phenyl)丙氧基]4-methoxyphenethyl) 1 h -咪唑盐酸盐)在结构上不同于已知的钙拮抗剂和显示选择性阻断RMCE与受体介导内部Ca2 +释放。人类血小板,中性粒细胞和内皮细胞含有荧光Ca2(+)指示剂染料quin2或fura-2,为了测量Ca2 +或Mn2 +条目通过RMCE以及Ca2 +释放内部商店。IC50(用量。生产50%抑制)抑制血小板刺激RMCE SK&F 96365的ADP或凝血酶分别是8.5 microM或11.7 microM;这些96365年SK&F浓度不影响内部Ca2 +释放。96365年SK&F类似的效果观察中性粒细胞的悬浮液和单一的内皮细胞。SK&F 96365也抑制agonist-stimulated Mn2 +进入血小板和中性粒细胞。SK&F 96365的影响是独立的细胞类型和受体激动剂,作为化合物,将调节受体后的事件。电压门控钙离子进入fura-2-loaded GH3(垂体)细胞和兔ear-artery平滑肌细胞下举行电压钳也抑制了SK&F 96365; however, the ATP-gated Ca2(+)-permeable channel of rabbit ear-artery smooth-muscle cells was unaffected by SK&F 96365. Thus SK&F 96365 (unlike the 'organic Ca2+ antagonists') shows no selectivity between voltage-gated Ca2+ entry and RMCE, although the lack of effect on ATP-gated channels indicates that it discriminates between different types of RMCE. The effects of SK&F 96365 on functional responses of cells thought to be dependent on Ca2+ entry via RMCE were also studied. Under conditions where platelet aggregation is dependent on stimulated Ca2+ entry via RMCE, the response was blocked by SK&F 96365 with an IC50 of 15.9 microM, which is similar to the IC50 of 8-12 microM observed for inhibition of RMCE. Adhesion and chemotaxis of neutrophils were also inhibited by SK&F 96365. SK&F 96365 is a useful tool to distinguish RMCE from internal Ca2+ release, and to probe the role of RMCE in mediating functional responses of cells. However, SK&F 96365 is not as potent (IC50 around 10 microM) or selective (also inhibits voltage-gated Ca2+ entry) as would be desirable, so caution must be exercised when using this compound.

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药物

skf - 96365自由基地