Alpha1-adrenoceptors are required for normal male sexual function.
Alpha1-adrenoceptors are required for normal male sexual function.
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DOI：
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发表时间：
2007
影响因子：
7.3
通讯作者：
A. Sanbe;Y. Tanaka;Y. Fujiwara;H. Tsumura;J. Yamauchi;S. Cotecchia;K. Koike;G. Tsujimoto;A. Tanoue
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文献类型：
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作者：
A. Sanbe;Y. Tanaka;Y. Fujiwara;H. Tsumura;J. Yamauchi;S. Cotecchia;K. Koike;G. Tsujimoto;A. Tanoue
背景和目的α 1肾上腺素受体拮抗剂广泛用于治疗高血压和与良性前列腺增生相关的下尿路症状。在这些副作用中，与其他这类药物相比，对α（1A）-肾上腺素受体具有相对选择性的药物更容易发生射精功能障碍。这表明α（1A）-肾上腺素受体可能有助于射精。然而，这还没有在分子水平上进行研究。实验方法使用α（1）-肾上腺素受体亚型选择性敲除（KO）小鼠（α（1A）-、α（1B）-和α（1D）-AR KO小鼠）表征每种α（1）-肾上腺素受体亚型的生理作用，因为可用的亚型特异性药物仅具有中等选择性。我们通过测定α 1肾上腺素受体亚型选择性KO小鼠和所有α 1肾上腺素受体亚型缺失的小鼠（α 1 AR三重KO小鼠）中的这些变量，分析了α 1肾上腺素受体在血压和血管反应以及射精中的作用。关键结果：α（1A）-肾上腺素受体敲除小鼠的妊娠率降低了50%，而这种降低在α（1）-肾上腺素受体三重敲除小鼠中显著增强。在α（1A）-肾上腺素受体敲除小鼠中，输精管对去甲肾上腺素的收缩张力显著降低，而在α（1）-肾上腺素受体三重敲除小鼠中，这种收缩完全消失。在电刺激的输精管中也观察到这种收缩性的衰减。结论和意义这些结果表明，α（1）-肾上腺素受体，特别是α（1A）-肾上腺素受体，是输精管正常收缩和精子射精所必需的，并具有生育功能。
BACKGROUND AND PURPOSE Alpha(1)-adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for alpha(1A)-adrenoceptors compared with other drugs of this class. This suggests that alpha(1A)-adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level. EXPERIMENTAL APPROACH The physiological contribution of each alpha(1)-adrenoceptor subtype was characterized using alpha(1)-adrenoceptor subtype-selective knockout (KO) mice (alpha(1A)-, alpha(1B)- and alpha(1D)-AR KO mice) since the subtype-specific drugs available are only moderately selective. We analysed the role of alpha(1)-adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in alpha(1)-adrenoceptor subtype-selective KO mice and in mice with all their alpha(1)-adrenoceptor subtypes deleted (alpha(1)-AR triple-KO mice). KEY RESULTS The pregnancy rate was reduced by 50% in alpha(1A)-adrenoceptor KO mice, and this reduction was dramatically enhanced in alpha(1)-adrenoceptor triple-KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in alpha(1A)-adrenoceptor KO mice, and this contraction was completely abolished in alpha(1)-adrenoceptor triple-KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens. CONCLUSIONS AND IMPLICATIONS These results demonstrate that alpha(1)-adrenoceptors, particularly alpha(1A)-adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.