• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells
【24h】

Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells

机译：西地那非，人海绵体平滑肌细胞中5型磷酸二酯酶的新型抑制剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In human corpus cavernosum, release of nitric oxide from the non-adrenergic, noncholinergic nerves and/or the endothelium activates guanylyl cyclase and increases intracellular cGMP levels. The increase in intracellular cGMP modulates intracellular calcium and in turn regulates smooth muscle contractility and erectile function. Phosphodiesterases play an important physiological role by regulating the intracellular levels of cyclic nucleotides. In this study, we investigated the kinetic parameters of inhibition of phosphodiesterase (PDE) type 5 (E.C. 3.1.4.35 3', 5'-cyclic GMP phosphodiesterase) by a novel, high affinity, selective PDE type 5 inhibitor, sildenafil, in soluble extracts of human corpus cavernosum smooth muscle cells. Sildenafil inhibited PDE type 5 cGMP-hydrolytic activity, in the crude extract (K-i=4-6 nM) and in partially purified preparations (K-i=2 nM) in a competitive manner, as determined by Dixon plots. Sildenafil (K-i=2-4 nM) was a more effective PDE type 5 inhibitor than zaprinast (K-i=250 nM). Stimulation of intracellular cGMP synthesis by the nitric oxide donor, sodium nitroprusside, resulted in less than a 5% increase in cGMP levels in the absence of sildenafil and a 35% increase in cGMP levels in the presence of sildenafil, in intact cells at physiological temperatures. These results are in accord with the clinical observations that sildenafil, taken orally, promotes penile erection through increased intracellular cGMP in response to sexual stimulation, potentiating smooth muscle relaxation. (C) 1998 Elsevier Science Inc. [References: 23]
机译：在人类海绵体中，从非肾上腺能，非胆碱能神经和/或内皮中释放一氧化氮可激活鸟苷酸环化酶并增加细胞内cGMP水平。细胞内cGMP的增加可调节细胞内钙，进而调节平滑肌的收缩力和勃起功能。磷酸二酯酶通过调节环核苷酸的细胞内水平发挥重要的生理作用。在这项研究中，我们研究了一种新型的，高亲和力，选择性的PDE 5型抑制剂西地那非在可溶状态下抑制5型磷酸二酯酶（PDE）（EC 3.1.4.35 3'，5'-环GMP磷酸二酯酶）的动力学参数。人海绵体平滑肌细胞提取物。西地那非以竞争方式抑制了粗提物（K-1 = 4-6 nM）和部分纯化的制剂（K-1 = 2 nM）中PDE 5型cGMP的水解活性，这是由狄克森曲线确定的。西地那非（K-i = 2-4 nM）是一种比zaprinast（K-i = 250 nM）更有效的PDE 5型抑制剂。在生理温度下完整细胞中，一氧化氮供体硝普钠刺激细胞内cGMP的合成导致在没有昔地那非的情况下cGMP水平增加不到5％，而在存在昔地那非的情况下cGMP水平增加了35％。 。这些结果与临床观察结果一致，即口服西地那非通过响应性刺激而增加细胞内cGMP来促进阴茎勃起，从而增强了平滑肌的松弛。 （C）1998 Elsevier Science Inc. [参考：23]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号