在含巯基化合物存在的情况下，FK409（一种自发释放一氧化氮的物质）释放一氧化氮（NO）的加速情况。

Acceleration of nitric oxide (NO) release from FK409, a spontaneous NO releaser, in the presence of sulfhydryl-bearing compounds.

作者信息

Fukuyama S, Hirasawa Y, Cox D, Koda S, Kita Y

机构信息

Analytical Research Laboratories, Fujisawa Pharmaceutical Co., Osaka, Japan.

出版信息

Pharm Res. 1995 Dec;12(12):1948-52. doi: 10.1023/a:1016248124104.

DOI:10.1023/a:1016248124104

PMID:8786971

Abstract

PURPOSE

Recently, we have reported that FK409 spontaneously releases nitric oxide (NO) in solution. In the present study, the influence of L-cysteine (Cys) and glutathione (GSH), which are typical sulfhydryl group-bearing compounds, on NO release from FK409 and biological action of FK409 was examined.

METHODS

We evaluated the effects of Cys and GSH on NO release from FK409 by nitrite analysis or detection with a chemiiluminesence analyzer. In a biological study, the influence of Cys on inhibition of rat platelet aggregation of FK409 was investigated. In addition, the above mentioned characteristics of FK409 were compared with those of isosorbide dinitrate (ISDN).

RESULTS

FK409 decomposed spontaneously with generation of nitrite in solution. Both Cys and GSH accelerated decomposition of FK409 and nitrite generation from FK409 in a concentration-dependent manner. When the NO levels in the headspace of FK409 solutions (0.5 mM) reached equilibrium with and without 25 mM Cys, the constant rate for NO release from FK409 in the presence of Cys was 13 times larger than that in the absence of Cys. In biological study, FK409 (100 microM) showed 56 and 90% inhibition of rat platelet aggregation in the absence and presence of 10 mM Cys, respectively, whereas ISDN (100 microM) showed 10 and 23% inhibition, respectively.

CONCLUSIONS

Decomposition of FK409 with generation of NO is spontaneous, and is accelerated in the presence of sulfhydryl group-bearing compounds, thereby potentiating the biological action of FK409.

摘要

目的

最近，我们报道了FK409在溶液中可自发释放一氧化氮（NO）。在本研究中，检测了典型的含巯基化合物L-半胱氨酸（Cys）和谷胱甘肽（GSH）对FK409释放NO及FK409生物学作用的影响。

方法

我们通过亚硝酸盐分析或化学发光分析仪检测评估了Cys和GSH对FK409释放NO的影响。在一项生物学研究中，研究了Cys对FK409抑制大鼠血小板聚集的影响。此外，将FK409的上述特性与硝酸异山梨酯（ISDN）的特性进行了比较。

结果

FK409在溶液中自发分解并生成亚硝酸盐。Cys和GSH均以浓度依赖性方式加速FK409的分解及从FK409生成亚硝酸盐。当FK409溶液（0.5 mM）顶空中的NO水平在有和没有25 mM Cys的情况下达到平衡时，存在Cys时FK409释放NO的恒定速率比不存在Cys时大13倍。在生物学研究中，FK409（100 microM）在不存在和存在10 mM Cys时分别对大鼠血小板聚集有56%和90%的抑制作用，而ISDN（100 microM）分别有10%和23%的抑制作用。