LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase.
LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase.
复制标题
LY 83583 干扰内皮源性舒张因子的释放并抑制可溶性鸟苷酸环化酶。
DOI：
--
复制
发表时间：
1988
影响因子：
3.5
通讯作者：
U. Förstermann
中科院分区：
文献类型：
--
作者：
A. Mülsch;R. Busse;S. Liebau;U. Förstermann
LY 83583（6-苯胺基-5，8-喹啉二酮）已被报道通过未知机制降低细胞内环GMP。本研究的目的是研究LY 83583对不同类型血管舒张的作用，并研究其作用机制。低浓度的LY 83583（小于或等于0.1 μ M）抑制乙酰胆碱或钙离子载体A23187诱导的兔主动脉条的内皮依赖性舒张。需要较高浓度（大于或等于0.3 μ M）才能部分抑制硝普钠和硝酸甘油的舒张作用。由异丙肾上腺素或毛喉素诱导的环AMP介导的舒张不受LY 83583（10 μ M）的影响。LY 83583干扰内皮依赖性舒张的部位用内皮衍生的舒张因子（EDRF）检查，所述内皮衍生的舒张因子（EDRF）从在微载体珠上生长的培养的内皮细胞释放，并通过用ATP或硫柳汞灌注刺激。灌流液中的EDRF检测由内皮剥脱段的兔股动脉，这与扩张反应，同时，在试管中的纯化的可溶性鸟苷酸环化酶（GC），这是由EDRF激活。当LY 83583被添加到含有谷胱甘肽的GC测定或培养的内皮细胞的灌流液中时，它不影响EDRF对可溶性GC的刺激，但它缓慢地逆转了动脉探测器段的扩张反应。用LY 83583（1 μ M）灌注培养的内皮细胞，快速且可逆地抑制EDRF释放。（250字处删节）
LY 83583 (6-anilino-5,8-quinolinedione) has been reported to lower intracellular cyclic GMP by an unknown mechanism. The objective of the present study was to investigate the effect of LY 83583 on different types of vasorelaxation and to study its mechanism of action. Low concentrations of LY 83583 (less than or equal to 0.1 microM) inhibited endothelium-dependent relaxations of rabbit aortic strips induced by acetylcholine or by the calcium ionophore A23187. Higher concentrations (greater than or equal to 0.3 microM) were required to produce partial inhibition of relaxation to sodium nitroprusside and glyceryl trinitrate. Cyclic AMP-mediated relaxations, induced by isoprenaline or forskolin, were not affected by LY 83583 (10 microM). The site of interference of LY 83583 with endothelium-dependent relaxation was examined with endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells that were grown on microcarrier beads and stimulated by superfusion with ATP or thimerosal. EDRF in the superfusate was detected by endothelium-denuded segments of rabbit femoral artery, which responded with dilation and, simultaneously, by purified soluble guanylate cyclase (GC) in test tubes, which was activated by EDRF. When LY 83583 was added to the glutathione-containing GC-assay or to the superfusate from cultured endothelial cells, it did not affect stimulation of soluble GC by EDRF but it slowly reversed the dilator response of the arterial detector segment. Superfusion of cultured endothelial cells with LY 83583 (1 microM), rapidly and reversibly inhibited EDRF release.(ABSTRACT TRUNCATED AT 250 WORDS)