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首页> 外文期刊>The journal of sexual medicine >The relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa.
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The relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa.

机译：尿鸟苷蛋白诱导的松弛和人海绵体中利钠肽受体的表达。

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INTRODUCTION: Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction. AIM: This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC). MAIN OUTCOME MEASURES: Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase-cyclic guanosine monophosphate (cGMP) pathway in HCC strips. METHODS: HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14-47 years) and strips were mounted in organ baths for isometric studies. RESULTS: ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4+/-4.0% and 49+/-4.8%, respectively. The relaxation is not affected by 30 microM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 microM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0+/-7.5-UGN vs. 98.6+/-1.4%-UGN+vardenafil; P<0.05). The relaxant effect was also partially (37.6%) blocked by the combination iberitoxin-apamin but was insensitive to glybenclamide. The expression of guanylate cyclase receptors (GC-A, GC-B, GC-C) and the expression of the natriuretic peptide "clearance" receptor (NPR-C) were confirmed by real-time polymerase chain reaction. The exposure of HCC strips to ANP (1 microM) and UGN (10 microM) significantly increased cGMP, but not cyclic adenosine monophosphate (cAMP) levels. CONCLUSIONS: UGN relaxes HCC strips by a guanylate cyclase and K(ca)-channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction.
机译：引言：利钠肽受体已被证明是治疗男性勃起功能障碍的潜在靶标。目的：本研究调查了房利钠肽（ANP）和尿鸟苷蛋白（UGN）的松弛作用，以及利尿肽受体在人海绵体（HCC）条上的表达。主要观察指标：定量分析利尿钠受体的表达和预收缩试纸条的松弛，以评估HCC试纸中的膜结合鸟苷酸环化酶-环鸟苷单磷酸（cGMP）途径。方法：肝癌是从尸体供体收集器官移植时（14-47岁）获得的，并将试纸条安装在器官浴中用于等距研究。结果：ANP和UGN都在HCC试纸上诱导了浓度依赖性的松弛，在300 nM处获得最大响应，分别对应于45.4 +/- 4.0％和49 +/- 4.8％。松弛不受30 microM 1H- [1,2,4]草酰二氮杂[4,3-a]喹喔啉-1-酮（ODQ）（可溶性鸟苷酸环化酶抑制剂）的影响，但被10 microM的isatin明显阻断，一种非特异性颗粒鸟苷酸环化酶（pGC）抑制剂。 UGN无法增强电场刺激（EFS）或乙酰胆碱引起的松弛。磷酸二酯酶5抑制剂伐地那非对该作用的增强作用增强了pGC激活和cGMP产生的潜在作用（55.0 +/- 7.5-UGN比98.6 +/- 1.4％-UGN + vardenafil; P <0.05 ）。松弛作用也被联合贝司毒素-阿帕米明部分阻断（37.6％），但对糖苷酰胺不敏感。通过实时聚合酶链反应确认鸟苷酸环化酶受体（GC-A，GC-B，GC-C）的表达和利钠肽“清除”受体（NPR-C）的表达。 HCC试纸暴露于ANP（1 microM）和UGN（10 microM）会显着增加cGMP，但不会增加环状单磷酸腺苷（cAMP）的水平。结论：UGN通过鸟苷酸环化酶和K（ca）通道依赖性机制松弛HCC条带。在HCC中获得的这些发现表明，利钠肽受体是开发用于治疗勃起功能障碍的新药物的潜在靶标。

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