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本文引用的文献

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Guide to Receptors and Channels (GRAC), 3rd edition.《受体与通道指南》（GRAC），第三版。
Br J Pharmacol. 2008 Mar;153 Suppl 2(Suppl 2):S1-209. doi: 10.1038/sj.bjp.0707746.
2
Comparison of efficacy between Tamsulosin and Finasteride on symptomatic Benign Prostatic Hyperplasia.坦索罗辛与非那雄胺治疗症状性良性前列腺增生的疗效比较。
Mymensingh Med J. 2007 Jul;16(2):154-9.
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"Phenotypic" pharmacology: the influence of cellular environment on G protein-coupled receptor antagonist and inverse agonist pharmacology.“表型”药理学：细胞环境对G蛋白偶联受体拮抗剂和反向激动剂药理学的影响
Biochem Pharmacol. 2007 Mar 15;73(6):737-51. doi: 10.1016/j.bcp.2006.09.005. Epub 2006 Sep 12.
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Clinical impact of tamsulosin on generic and symptom-specific quality of life for benign prostatic hyperplasia patients: using international prostate symptom score and Rand Medical Outcomes Study 36-item Health Survey.坦索罗辛对良性前列腺增生症患者总体及症状特异性生活质量的临床影响：采用国际前列腺症状评分和兰德医疗结局研究36项健康调查
Int J Urol. 2006 Sep;13(9):1202-6. doi: 10.1111/j.1442-2042.2006.01594.x.
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Alpha1L-adrenoceptors mediate contractions of the isolated mouse prostate.α1L-肾上腺素能受体介导离体小鼠前列腺的收缩。
Eur J Pharmacol. 2006 Jul 1;540(1-3):155-61. doi: 10.1016/j.ejphar.2006.04.016. Epub 2006 Apr 28.
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Efficacy and safety of tamsulosin for benign prostatic hyperplasia: clinical experience in the primary care setting.
Curr Med Res Opin. 2006 Apr;22(4):721-30. doi: 10.1185/030079906X96443.
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Evaluation of the mouse prostate as a suitable model for the study of human prostate function.评估小鼠前列腺作为研究人类前列腺功能的合适模型。
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Pharmacological characterization of alpha1-adrenoceptors in mouse isolated femoral small arteries.小鼠离体股小动脉中α1肾上腺素能受体的药理学特性
Eur J Pharmacol. 2004 Oct 25;503(1-3):155-63. doi: 10.1016/j.ejphar.2004.09.046.
9
Adenosine 5'-triphosphate and noradrenaline are excitatory cotransmitters to the fibromuscular stroma of the guinea pig prostate gland.三磷酸腺苷和去甲肾上腺素是豚鼠前列腺纤维肌基质的兴奋性共递质。
Eur J Pharmacol. 2004 Sep 24;499(3):335-44. doi: 10.1016/j.ejphar.2004.07.080.
10
High-affinity interactions between human alpha1A-adrenoceptor C-terminal splice variants produce homo- and heterodimers but do not generate the alpha1L-adrenoceptor.人α1A -肾上腺素能受体C末端剪接变体之间的高亲和力相互作用产生同二聚体和异二聚体，但不会生成α1L -肾上腺素能受体。
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α1A -肾上腺素能受体基因是小鼠前列腺分离制剂中α1L -肾上腺素能受体介导反应所必需的。

The alpha1A-adrenoceptor gene is required for the alpha1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate.

作者信息

Gray Kt, Short Jl, Ventura S

机构信息

Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

出版信息

Br J Pharmacol. 2008 Sep;155(1):103-9. doi: 10.1038/bjp.2008.245. Epub 2008 Jun 16.

DOI:10.1038/bjp.2008.245
PMID:18552869
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2527847/
Abstract

BACKGROUND AND PURPOSE

This study investigated whether deletion of the alpha1A-adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by alpha1L-adrenoceptors, which are thought to be a functional phenotype of alpha1A-adrenoceptor.

EXPERIMENTAL APPROACH

Prostate tissues from alpha1A-adrenoceptor knockout mice which were homozygous (alpha1A -/-) and heterozygous (alpha1A +/-) for the disrupted alpha1A-adrenoceptor gene, as well as wild-type (alpha1A +/+) littermates were mounted in glass-isolated organ baths. Electrical field stimulation of nerves and exogenous application of noradrenaline were used to investigate the effects of alpha1A-adrenoceptor disruption on prostate contractility.

KEY RESULTS

Frequency-response curves to electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1-20 Hz) yielded frequency-dependent contractions. At frequencies of 10 and 20 Hz, prostates from alpha1A -/- mice elicited an approximately 30% decreased response compared with prostates from alpha(1A)+/+ mice. Prazosin (0.3 muM) attenuated responses to electrical field stimulation in prostates from alpha1A +/+ and alpha1A +/- mice but not from alpha1A -/- mice. Increasing concentrations of exogenously administered noradrenaline (10 nM-1 mM) produced mean concentration-response curves in prostates from alpha1A +/+ and alpha1A +/- mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from alpha1A -/- mice compared with alpha1A +/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes.

CONCLUSIONS AND IMPLICATIONS

alpha1L-Adrenoceptor-mediated responses in mouse prostate are abolished in alpha1A -/- mice, demonstrating that the alpha1A-adrenoceptor gene is essential to the manifestation of the prostatic alpha1L-adrenoceptor phenotype. This implies that alpha1L-adrenoceptors are indeed a functional phenotype of alpha1A-adrenoceptor.

摘要

背景与目的

本研究调查了α1A -肾上腺素能受体基因的缺失是否会影响小鼠前列腺对去甲肾上腺素的收缩反应。已知小鼠前列腺对去甲肾上腺素的反应是由α1L -肾上腺素能受体介导的，而α1L -肾上腺素能受体被认为是α1A -肾上腺素能受体的一种功能表型。

实验方法

将α1A -肾上腺素能受体基因敲除的纯合子（α1A -/-）和杂合子（α1A +/-）小鼠以及野生型（α1A +/+）同窝小鼠的前列腺组织安装在玻璃隔离的器官浴槽中。通过电场刺激神经和外源性应用去甲肾上腺素来研究α1A -肾上腺素能受体缺失对前列腺收缩性的影响。

主要结果

对电场刺激（脉冲持续时间0.5毫秒，60伏，0.1 - 20赫兹）的频率 - 反应曲线产生了频率依赖性收缩。在10和20赫兹频率下，与α1A +/+小鼠的前列腺相比，α1A -/-小鼠的前列腺引发的反应降低了约30%。哌唑嗪（0.3微摩尔）减弱了α1A +/+和α1A +/-小鼠前列腺对电场刺激的反应，但对α1A -/-小鼠的前列腺无此作用。外源性给予去甲肾上腺素浓度增加（10纳摩尔 - 1毫摩尔）在α1A +/+和α1A +/-小鼠的前列腺中产生平均浓度 - 反应曲线，二者无差异。与α1A +/+小鼠相比，α1A -/-小鼠的前列腺对去甲肾上腺素的最大反应降低了约80%。哌唑嗪减弱了所有基因型对去甲肾上腺素的反应。

结论与意义

α1A -/-小鼠中α1L -肾上腺素能受体介导的小鼠前列腺反应消失，表明α1A -肾上腺素能受体基因对于前列腺α1L -肾上腺素能受体表型的表现至关重要。这意味着α1L -肾上腺素能受体确实是α1A -肾上腺素能受体的一种功能表型。