阿片样肽（内源性中性内肽酶抑制剂）在泌尿生殖系统平滑肌生物学中的作用。
The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology.
作者信息
Davies Kelvin Paul
机构信息
Albert Einstein College of Medicine, Department of Urology and Institute of Smooth Muscle Biology, Bronx, NY 10461, USA.
出版信息
J Sex Med. 2009 Mar;6 Suppl 3(Suppl 3):286-91. doi: 10.1111/j.1743-6109.2008.01186.x.
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.
引言
阿片肽是一类新发现的肽，可作为强效内源性中性内肽酶（NEP）抑制剂。近期报道表明它们在勃起生理过程中发挥重要作用。
目的
本文综述了近期的研究进展，这些进展加深了我们对阿片肽家族在勃起生理中作用的理解。
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时，Vcsa1是大鼠海绵体中下调最明显的基因之一。定量实时聚合酶链反应表明，在至少三种导致ED的疾病模型（糖尿病、衰老和海绵体神经[CN]横断）中，大鼠海绵体中的Vcsa1表达下调。人类阿片肽家族基因（hSMR3A/B和ProL1）也是ED患者勃起功能的标志物。
主要观察指标
读者将了解到关于阿片肽在泌尿生殖系统平滑肌生物学中作用的最新研究。
结果
这些观察结果提示，编码阿片肽的基因（及其潜在的肽产物）可作为ED的标志物。在衰老大鼠中过表达Vcsa1的质粒基因转移以及阴茎内注射唾液吗啡，均导致勃起功能改善。在器官浴研究中，我们证明唾液吗啡可使海绵体平滑肌（CSM）的舒张速率增加。我们还证明，在体外，Vcsa1可引起G蛋白偶联受体（GPCRs）表达的变化。这使我们推测，Vcsa1对勃起生理的作用可能是通过作为NEP抑制剂来松弛CSM，从而延长肽类激动剂在其GPCRs上的作用。
结论
总体而言，越来越多的证据表明阿片肽在调节CSM张力进而调节勃起功能中发挥作用。
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