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不同磷酸二酯酶基因在人海绵体平滑肌中的表达

Expression of different phosphodiesterase genes in human cavernous smooth muscle.

作者信息

Küthe A, Wiedenroth A, Mägert H J, Uckert S, Forssmann W G, Stief C G, Jonas U

机构信息

Department of Urology, Hannover Medical School and Lower Saxony Institute for Peptide Research, Hannover, Germany.

出版信息

J Urol. 2001 Jan;165(1):280-3. doi: 10.1097/00005392-200101000-00079.

Abstract

PURPOSE

Knowledge of intracellular signal propagation in smooth muscle tone regulation is of major importance in the understanding of the physiology of penile erection, and the development of new and selective pharmacological agents for the treatment of related disorders. Since phosphodiesterases (PDE) are key enzymes of the signaling pathway, we elucidate their presence and potential functional relevance in human cavernous tissue.

MATERIALS AND METHODS

To identify PDE messenger RNA in human cavernous tissue, we constructed primers for 14 published PDE isoforms. Expression of the genes was then analyzed by reverse transcriptase polymerase chain reaction under standard conditions and by subsequent sequencing.

RESULTS

Messenger RNA was detected in human corpus cavernosum for the human phosphodiesterase isoenzymes and isoforms PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE7A, PDE8A and PDE9A.

CONCLUSIONS

A total of 13 PDE genes were expressed in human cavernous tissue, indicating a role of these enzymes in penile erection regulation. The intracellular mechanisms of hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate by PDEs are more complex than assumed previously. These findings open up new possibilities in the development of drugs for the treatment of erectile dysfunction.

摘要

目的

了解平滑肌张力调节中的细胞内信号传导,对于理解阴茎勃起的生理学以及开发用于治疗相关疾病的新型选择性药物至关重要。由于磷酸二酯酶(PDE)是信号通路中的关键酶,我们阐明了它们在人海绵体组织中的存在及其潜在的功能相关性。

材料与方法

为了鉴定人海绵体组织中的PDE信使核糖核酸(mRNA),我们为14种已发表的PDE同工型构建了引物。然后在标准条件下通过逆转录聚合酶链反应并随后进行测序来分析基因的表达。

结果

在人海绵体中检测到了人磷酸二酯酶同工酶和同工型PDE1A、PDE1B、PDE1C、PDE2A、PDE3A、PDE4A、PDE4B、PDE4C、PDE4D、PDE5A、PDE7A、PDE8A和PDE9A的信使核糖核酸。

结论

共有13种PDE基因在人海绵体组织中表达,表明这些酶在阴茎勃起调节中发挥作用。PDE水解环磷酸腺苷和环磷酸鸟苷的细胞内机制比以前认为的更为复杂。这些发现为开发治疗勃起功能障碍的药物开辟了新的可能性。

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