首页> 外文期刊>The journal of sexual medicine >The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology.
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The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology.

机译:阿片吗啡(内源性中性内肽酶抑制剂)在泌尿生殖道平滑肌生物学中的作用。

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INTRODUCTION: The opiorphins are a newly characterized class of peptides that act as potent endogenous neutral endopeptidase (NEP) inhibitors. Recent reports have suggested that they play an important role in erectile physiology. AIM: This article reviews recent developments that increase our understanding of the role of the opiorphin family of peptides in erectile physiology. METHODS: During a microarray screen of gene changes that occur in a rat diabetic model of erectile dysfunction (ED), Vcsa1 was one of the most down-regulated genes in the rat corpora. Quantitative real-time polymerase chain reaction demonstrated that in at least three models of diseases that result in ED (diabetes, aging, and cavernous nerve [CN] transection), Vcsa1 was down-regulated in the rat corpora. The human opiorphin family of genes (hSMR3A/B and ProL1) also acts as markers of erectile function in patients with ED. MAIN OUTCOME MEASURES: The reader will be informed of the most current research regarding the role of opiorphins in urogenital smooth muscle biology. RESULTS: These observations led to the suggestion that genes encoding opiorphins (and potentially their peptide products) can act as markers of ED. Gene transfer of plasmids overexpressing Vcsa1 in aging rats, as well as intracorporal injection of sialorphin, led to an improvement in erectile function. In organ bath studies, we demonstrated that sialorphin can cause increased rates of relaxation of corporal smooth muscle (CSM). We have also demonstrated that in vitro, Vcsa1 causes changes in the expression of G-protein-coupled receptors (GPCRs). This has led us to suggest that the action of Vcsa1 on erectile physiology may act through relaxation of CSM by its ability to act as an inhibitor of NEP, therefore prolonging the action of peptide agonists at their GPCRs. CONCLUSIONS: Overall, there is a growing body of evidence that the opiorphins play a role in regulating CSM tone and thereby erectile function.
机译:简介:阿片吗啡是一类新近鉴定的肽,可作为有效的内源性中性内肽酶(NEP)抑制剂。最近的报道表明它们在勃起生理中起着重要作用。目的:本文回顾了最近的发展,这些发展使我们更加了解了opiorphin肽家族在勃起生理中的作用。方法:在对大鼠勃起功能障碍(ED)糖尿病模型中发生的基因变化进行微阵列筛选期间,Vcsa1是大鼠语料库中表达最下调的基因之一。实时定量聚合酶链反应表明,在至少三种导致ED的疾病模型(糖尿病,衰老和海绵状神经[CN]横切)中,Vcsa1在大鼠语料库中下调。人类opiorphin基因家族(hSMR3A / B和ProL1)也可作为ED患者勃起功能的标志物。主要观察指标:将向读者介绍有关阿片吗啡在泌尿生殖道平滑肌生物学中的作用的最新研究。结果:这些观察结果提示,编码阿片吗啡(可能是其肽产物)的基因可以作为ED的标记。衰老大鼠中过表达Vcsa1的质粒的基因转移以及唾液内啡肽的体内注射导致勃起功能的改善。在器官浴研究中,我们证明了唾液酸蛋白可导致体表平滑肌(CSM)的松弛率增加。我们还证明,在体外,Vcsa1会导致G蛋白偶联受体(GPCR)的表达发生变化。这已导致我们提出,Vcsa1对勃起生理的作用可能是通过放松CSM发挥其作为NEP抑制剂的能力而起作用的,从而延长了肽激动剂在其GPCR上的作用。结论:总的来说,越来越多的证据表明阿片吗啡在调节CSM音调和勃起功能中起作用。

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