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阴茎海绵体中C型利钠肽依赖性鸟苷酸环化酶偶联受体的存在及其生物学活性

Presence and biological activity of C-type natriuretic peptide-dependent guanylate cyclase-coupled receptor in the penile corpus cavernosum.

作者信息

Kim S Z, Kim S H, Park J K, Koh G Y, Cho K W

机构信息

Department of Physiology, Medical School, Jeonbug National University, Jeonju, Republic of Korea.

出版信息

J Urol. 1998 May;159(5):1741-6. doi: 10.1097/00005392-199805000-00104.

DOI:10.1097/00005392-199805000-00104
PMID:9554404
Abstract

PURPOSE

To investigate the presence of C-type natriuretic peptide 1-22 (CNP)-dependent guanylyl cyclase (GC)-coupled receptor and its biological function in the penile erectile smooth muscle.

MATERIALS AND METHODS

Experiments have been done in rabbit and rat to detect cyclic GMP (cGMP) generation by the activation of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to localize precise receptor using a quantitative in vitro autoradiography of the snap frozen sections, to define natriuretic peptide receptor (NPR) mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to monitor changes of erectile smooth muscle tone by NPs in the penile tissue strips.

RESULTS

Productions of cGMP by particulate GC in the corpus cavernosum membranes of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP) and brain natriuretic peptide 1-26 (BNP) with a rank order of potency of CNP > BNP > ANP. HS-142-1, a selective antagonist for the GC-coupled NPR, inhibited the CNP-stimulated cGMP production in corpus cavernosal membrane of rabbit and rat. Specific 125I-(Tyr[0])-CNP bindings were localized in the corpus cavernosal smooth muscle of rabbit with Kd of 19.92+/-3.38 nM. and Bmax of 734.64+/-139.63 amol./mm2. B-subtype of NPR mRNA was detected in the penile corpus cavernosum of rat using RT-PCR technique. CNP relaxed the smooth muscle contracted by Nomega-nitro-L-arginine methylester (L-NAME).

CONCLUSIONS

These results suggest for the first time that CNP modulates the erectile smooth muscle tone of penis by predominant activation of B-subtype of NPR with augmentation of cGMP production via particulate GC.

摘要

目的

研究C型利钠肽1 - 22(CNP)依赖性鸟苷酸环化酶(GC)偶联受体在阴茎勃起平滑肌中的存在及其生物学功能。

材料与方法

在兔和大鼠中进行实验,以检测利钠肽(NP)激活海绵体膜中的颗粒性GC所产生的环磷酸鸟苷(cGMP),通过对速冻切片进行定量体外放射自显影来定位精确的受体,使用逆转录聚合酶链反应(RT-PCR)技术确定利钠肽受体(NPR)mRNA,并监测NP对阴茎组织条中勃起平滑肌张力的影响。

结果

兔和大鼠海绵体膜中颗粒性GC产生cGMP受到CNP、心房利钠肽1 - 28(ANP)和脑利钠肽1 - 26(BNP)的刺激,其效力顺序为CNP > BNP > ANP。HS - 142 - 1,一种GC偶联NPR的选择性拮抗剂,抑制了兔和大鼠海绵体膜中CNP刺激的cGMP产生。特异性的125I -(Tyr[0])- CNP结合定位于兔海绵体平滑肌,解离常数(Kd)为19.92±3.38 nM,最大结合容量(Bmax)为734.64±139.63 amol./mm2。使用RT-PCR技术在大鼠阴茎海绵体中检测到NPR mRNA的B亚型。CNP使由Nω-硝基-L-精氨酸甲酯(L-NAME)收缩的平滑肌舒张。

结论

这些结果首次表明,CNP通过主要激活NPR的B亚型并通过颗粒性GC增加cGMP的产生来调节阴茎勃起平滑肌张力。

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