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研究各种可能影响平滑肌张力的药物对人离体精囊组织的影响。

Characterization of the effects of various drugs likely to affect smooth muscle tension on isolated human seminal vesicle tissue.

机构信息

Department of Urology, University of Indonesia School of Medicine, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

出版信息

Urology. 2010 Apr;75(4):974-8. doi: 10.1016/j.urology.2009.09.034. Epub 2009 Dec 6.

DOI:10.1016/j.urology.2009.09.034
PMID:19969333
Abstract

OBJECTIVES

To investigate the effects of different classes of drugs on the isometric tension of isolated human seminal vesicle (SV) tissue. The contractility of human SV contributes to the process of seminal emission during ejaculation. Different endogenous compounds, such as serotonin (5-HT), adenosine triphosphate (ATP), and nitric oxide, have been suggested to be involved in the control of contraction and relaxation of human SV smooth muscle. However, only limited data are available regarding the effects of compounds known to affect smooth musculature on SV contractile activity.

METHODS

Using the organ bath technique, the effects of increasing concentrations (10 nm-1 microm/10 microm) of norepinephrine (NE), phenylephrine, endothelin 1, ATP, and 5-HT on human SV tissue at basal tension were studied. In another set-up, SV strip preparations were preincubated with prazosin (alpha-adrenergic blocker), nifedipine and verapamil (Ca(2+)-channel blockers), 2-aminoethoxydiphenyl borate [inositol 1,4,5-trisphosphate (IP(3)) antagonist], cromakalim (K(+)-channel opener), or Y-27632 (ROK inhibitor) (1 microm each, for 10 minutes), followed by the application of NE (0.1 microM, 1 microM, and 10 microm).

RESULTS

SV smooth muscle was most effectively contracted by NE (mean = 75% of calibrated scale), phenylephrine (mean = 82% of calibrated scale), and endothelin 1 (mean = 70% calibrated scale), whereas only minor responses to ATP (mean = 10.65% calibrated scale) and 5-HT (mean = 6.3% calibrated scale) were observed. The contraction induced by NE was significantly inhibited after pre-exposure of the tissue to prazosin (-92.4%), cromakalim (-83.7%), 2-aminoethoxydiphenyl borate (-43.1%), Y-27632 (-42.8%), and nifedipine (-32.7%).

CONCLUSIONS

alpha-adrenoceptor antagonism, activation of potassium channels, and inhibition of Rho-kinase decrease the sympathetic contraction of SV smooth muscle. This might be of significance with regard to the identification of new pharmacologic avenues to affect the male ejaculatory system.

摘要

目的

研究不同类别的药物对离体人精囊(SV)组织等长张力的影响。人 SV 的收缩有助于射精过程中的精液排放。已有研究表明,一些内源性化合物,如 5-羟色胺(5-HT)、三磷酸腺苷(ATP)和一氧化氮,可能参与人 SV 平滑肌的收缩和舒张控制。然而,关于已知影响平滑肌的化合物对 SV 收缩活性的影响,仅有有限的数据。

方法

采用器官浴技术,研究浓度递增(10nm-1μm/10μm)的去甲肾上腺素(NE)、苯肾上腺素、内皮素 1、ATP 和 5-HT 对基础张力下人 SV 组织的影响。在另一组实验中,SV 条带制剂先用哌唑嗪(α-肾上腺素能阻滞剂)、硝苯地平、异搏定(Ca(2+)通道阻滞剂)、2-氨基乙氧基二苯硼酸盐[三磷酸肌醇(IP(3))拮抗剂]、克罗卡林(K(+)通道开放剂)或 Y-27632(ROK 抑制剂)(每种 1μm,10 分钟)预孵育,然后应用 NE(0.1μm、1μm 和 10μm)。

结果

SV 平滑肌对 NE(平均收缩 75%的标度)、苯肾上腺素(平均收缩 82%的标度)和内皮素 1(平均收缩 70%的标度)的收缩作用最有效,而对 ATP(平均收缩 10.65%的标度)和 5-HT(平均收缩 6.3%的标度)的反应则较小。组织预先暴露于哌唑嗪(-92.4%)、克罗卡林(-83.7%)、2-氨基乙氧基二苯硼酸盐(-43.1%)、Y-27632(-42.8%)和硝苯地平(-32.7%)后,NE 诱导的收缩明显受到抑制。

结论

α-肾上腺素能受体拮抗、钾通道激活和 Rho-激酶抑制降低了 SV 平滑肌的交感收缩。这对于确定影响男性射精系统的新药理途径可能具有重要意义。

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