Yono Makoto, Yamamoto Yasuhiro, Imanishi Aya, Fukagawa Atsushi, Latifpour Jamshid, Yoshida Masaki
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
BJU Int. 2009 Jun;103(12):1680-5. doi: 10.1111/j.1464-410X.2009.08364.x. Epub 2009 Feb 10.
To investigate the short- and long-term effects of silodosin, a selective alpha(1A)-adrenoceptor antagonist, on spontaneous seminal emission by isolated rats and on the properties of alpha(1)-adrenoceptor subtypes in the rat seminal vesicle, as silodosin produces a relatively high incidence rate of abnormal ejaculation and chronic administration of receptor antagonists causes an up-regulation in the targeted receptor.
Rats were treated with two doses (0.1 and 3 mg/kg/day) of silodosin orally for 3 or 30 days. Spontaneous seminal emission was studied during the 3-day observation period before completing treatment. The expression levels of alpha(1A), alpha(1B) and alpha(1D)-adrenoceptor mRNAs in the rat seminal vesicle and prostate were quantified by real-time reverse transcription-polymerase chain reaction using SYBR Green I.
The administration of two doses of silodosin for 3 or 30 days caused a significant dose-dependent reduction in the number of ejaculatory plugs and in their dry weight. However, in rats receiving the low dose of silodosin the inhibitory effect of the drug on spontaneous seminal emission diminished significantly with chronic usage over time. Although short-term administration of silodosin did not affect expression levels of any alpha(1)-adrenoceptor subtype mRNAs in the rat seminal vesicle and prostate, long-term administration of silodosin caused a significant up-regulation in the mRNA expression of alpha(1A)-adrenoceptor in a tissue-dependent manner.
Silodosin-induced up-regulation of alpha(1A)-adrenoceptor mRNA in the rat seminal vesicle might indicate potential differences in the inhibitory effect of this drug on ejaculatory function with chronic usage over time.
研究选择性α(1A)-肾上腺素能受体拮抗剂西洛多辛对离体大鼠自发性射精的短期和长期影响，以及对大鼠精囊α(1)-肾上腺素能受体亚型特性的影响，因为西洛多辛会导致较高的异常射精发生率，且长期给予受体拮抗剂会引起靶向受体上调。
大鼠口服两种剂量（0.1和3毫克/千克/天）的西洛多辛，持续3天或30天。在完成治疗前的3天观察期内研究自发性射精情况。使用SYBR Green I通过实时逆转录-聚合酶链反应对大鼠精囊和前列腺中α(1A)、α(1B)和α(1D)-肾上腺素能受体mRNA的表达水平进行定量。
给予两种剂量的西洛多辛3天或30天导致射精栓数量及其干重显著呈剂量依赖性减少。然而，在接受低剂量西洛多辛的大鼠中，随着时间的推移，药物对自发性射精的抑制作用会随着长期使用而显著减弱。虽然短期给予西洛多辛不影响大鼠精囊和前列腺中任何α(1)-肾上腺素能受体亚型mRNA的表达水平，但长期给予西洛多辛会以组织依赖性方式导致α(1A)-肾上腺素能受体mRNA表达显著上调。
西洛多辛诱导大鼠精囊中α(1A)-肾上腺素能受体mRNA上调可能表明随着时间的推移长期使用该药物对射精功能的抑制作用存在潜在差异。
