The Beta-3 Adrenoceptor Agonist, Mirabegron Relaxes Isolated Prostate From Human and Rabbit: New Therapeutic Indication?
The Beta-3 Adrenoceptor Agonist, Mirabegron Relaxes Isolated Prostate From Human and Rabbit: New Therapeutic Indication?
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DOI：
10.1002/pros.22930
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发表时间：
2015-03-01
期刊：
影响因子：
2.8
通讯作者：
Monica, Fabiola Z.
中科院分区：
文献类型：
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作者：
Calmasini, Fabiano B.;Candido, Tuany Z.;Monica, Fabiola Z.
pha1(1)-阻滞剂、5- α还原酶和磷酸二酯酶5型抑制剂是目前可用于治疗良性前列腺增生（BPH）的药物类别。Mirabegron是一种β -3肾上腺素能受体（3-AR）激动剂，已被批准用于治疗膀胱过动症，可能成为BPH治疗的一种新的治疗选择。本研究旨在评价mirabegron对人和家兔前列腺平滑肌的体外作用。方法对家兔前列腺进行电场刺激（EFS）诱导的收缩，并在苯肾上腺素预收缩组织中测定mirabegron的浓度-反应曲线（CRC）。测定药效（pEC(50)）和最大反应（E-max）值。在人类前列腺中，对苯肾上腺素的结直肠癌是在不存在和存在米拉贝隆的情况下进行的。对3-AR进行免疫组化分析。结果免疫组化分析显示，在人前列腺过渡区存在3-AR， mirabegron可使苯肾上腺素引起的收缩减少42%。在家兔前列腺中，mirabegron产生浓度依赖性松弛(pEC(50): 6.010.12；E-max: 106 +/- 3%)，完全抵抗1-AR和2-AR的阻断。3-AR阻滞剂L748,337导致mirabetron诱导的弛缓向右移动6倍。Mirabegron （10M）减少了63%的efs引起的收缩。一氧化氮（L-NAME）和可溶性鸟苷酸环化酶（ODQ）抑制剂以及K+通道阻滞剂（apamin, charybdotoxin, glibenclamide， tetra乙基铵）的混合物都不能显著影响mirabegron诱导的家兔松弛。结论mirabegron具有放松前列腺平滑肌的作用，为其联合1-受体阻滞剂或PDE5抑制剂治疗前列腺增生提供了实验支持。中华医学杂志（英文版），2015。(c) 2014 Wiley期刊公司
BACKGROUNDAlpha1 (1)-blockers, 5-alpha reductase and phosphodiesterase type-5 inhibitors are pharmacological classes currently available for benign prostatic hyperplasia (BPH) treatment. Mirabegron, a beta-3 adrenoceptor (3-AR) agonist has been approved for the therapy of overactive bladder and may constitute a new therapeutic option for BPH treatment. This study is aimed to evaluate the in vitro effects of mirabegron in human and rabbit prostatic smooth muscle.METHODSIn rabbit prostate, electrical field stimulation (EFS)-induced contraction and concentration-response curve (CRC) to mirabegron in phenylephrine pre-contracted tissues were carried out. The potency (pEC(50)) and maximal response (E-max) values were determined. In human prostate, CRC to phenylephrine was carried out in the absence and presence of mirabegron. Immunohistochemistry analysis for 3-AR was also carried out.RESULTSIn human prostate, immunohistochemistry analysis revealed the presence of 3-AR on the transition zone and mirabegron reduced by 42% the phenylephrine-induced contractions. In rabbit prostate, mirabegron produced concentration-dependent relaxations (pEC(50): 6.010.12; E-max: 106 +/- 3%), which were fully resistant to the blockade of 1-AR and 2-AR. The 3-AR blocker L748,337 caused a six-fold rightward shift in mirabegron-induced relaxations. Mirabegron (10M) reduced by 63% the EFS-induced contractions. Inhibitors of nitric oxide (L-NAME) and of soluble guanylate cyclase (ODQ) along with a cocktail of K+ channel blockers (apamin, charybdotoxin, glibenclamide, tetraethylammonium) all failed to significantly affect the mirabegron-induced rabbit relaxations.CONCLUSIONMirabegron relaxes prostatic smooth muscle, providing an experimental support for the clinical investigation of its combination with an 1-blockers or PDE5 inhibitors in the treatment of BPH. Prostate 75:440-447, 2015. (c) 2014 Wiley Periodicals, Inc.