α7烟碱型乙酰胆碱受体在大鼠海绵体中的表达、定位及功能

The expression, localization and function of α7 nicotinic acetylcholine receptor in rat corpus cavernosum.

作者信息

Faghir-Ghanesefat Hedyeh, Rahimi Nastaran, Yarmohammadi Fatemeh, Mokhtari Tahmineh, Abdollahi Ali Reza, Ejtemaei Mehr Shahram, Dehpour Ahmad R

机构信息

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Pharm Pharmacol. 2017 Dec;69(12):1754-1761. doi: 10.1111/jphp.12806. Epub 2017 Aug 24.

DOI:10.1111/jphp.12806

PMID:28836276

Abstract

OBJECTIVES

Alpha7 nicotinic acetylcholine receptor (α7-nAChR), an emerging pharmacological target for a variety of medical conditions, is expressed in the most mammalian tissues with different effects. So, this study was designed to investigate the expression, localization and effect of α7-nAChR in rat corpus cavernosum (CC).

METHODS & KEY FINDINGS: Reverse transcription polymerase chain reaction (RT-PCR) revealed that α7-nAChR was expressed in rat CC and double immunofluorescence studies demonstrated the presence of α7-nAChR in corporal neurons. The rat CC segments were mounted in organ bath chambers and contracted with phenylephrine (0.1 μm -300 μm) to investigate the relaxation effect of electrical field stimulation (EFS,10 Hz) assessed in the presence of guanethidine (adrenergic blocker, 5 μm) and atropine (muscarinic cholinergic blocker, 1 μm) to obtain non-adrenergic non-cholinergic (NANC) response. Cumulative administration of nicotine significantly potentiated the EFS-induced NANC relaxation (-log EC50 = 7.5 ± 0.057). Whereas, the potentiated NANC relaxation of nicotine was significantly inhibited with different concentrations of methyllycaconitine citrate (α7-nAChR antagonist, P < 0.05) in preincubated strips. L-NAME (non-specific nitric oxide synthase inhibitor, 1 μm) completely blocked the neurogenic relaxation induced by EFS plus nicotine.

CONCLUSION

To conclude α7-nAChR is expressed in rat CC and modulates the neurogenic relaxation response to nicotine.

摘要

目的

α7烟碱型乙酰胆碱受体（α7-nAChR）是多种医学病症中一个新出现的药理学靶点，在大多数哺乳动物组织中均有表达且具有不同作用。因此，本研究旨在探究α7-nAChR在大鼠阴茎海绵体（CC）中的表达、定位及作用。

方法与主要发现

逆转录聚合酶链反应（RT-PCR）显示α7-nAChR在大鼠CC中表达，双重免疫荧光研究证明α7-nAChR存在于海绵体神经元中。将大鼠CC节段安装在器官浴槽中，用去氧肾上腺素（0.1μm - 300μm）使其收缩，以研究电场刺激（EFS，10Hz）的舒张作用，该舒张作用在胍乙啶（肾上腺素能阻滞剂，5μm）和阿托品（毒蕈碱型胆碱能阻滞剂，1μm）存在的情况下进行评估，以获得非肾上腺素能非胆碱能（NANC）反应。累积给予尼古丁可显著增强EFS诱导的NANC舒张作用（-log EC50 = 7.5 ± 0.057）。然而，在预孵育的条带上，不同浓度的柠檬酸甲基lycaconitine（α7-nAChR拮抗剂，P < 0.05）可显著抑制尼古丁增强的NANC舒张作用。L-NAME（非特异性一氧化氮合酶抑制剂，1μm）完全阻断了EFS加尼古丁诱导的神经源性舒张。