Department of Urology, Ludwig-Maximilians University, Munich, Germany.
Life Sci. 2012 Mar 10;90(11-12):446-53. doi: 10.1016/j.lfs.2012.01.002. Epub 2012 Jan 17.
Besides their role in contraction, α1-adrenoceptors may be involved in prostate hyperplasia. This would require receptor signaling by growth-promoting pathways. Akt (syn. Protein kinase B) is an important regulator of growth and differentiation.
To investigate whether α1-adrenoceptors in the human prostate activate Akt.
Prostate tissue was obtained from patients undergoing radical prostatectomy. Akt expression was investigated by RT-PCR, Western blot, and immunohistochemistry. Akt activation by noradrenaline (30 μM) and phenylephrine (10 μM) was assessed by Western blot analyses with a phospho-specific antibody. The effects of the Akt inhibitors FPA-124 and 10-DEBC on phenylephrine-, noradrenaline- and electric field stimulation- (EFS-) induced contraction were studied in myographic measurements.
mRNA of all three Akt isoforms (Akt1, Akt2, Akt3) was detected by RT-PCR in all prostate samples (n=6 patients). Protein expression was confirmed by Western blot analysis (n=8 patients). Immunohistochemical staining for Akt revealed strong immunoreactivity in prostate smooth muscle cells (n=5 patients). Stimulation of prostate tissues with noradrenaline (30 μM, n=8 patients) or phenylephrine (10 μM, n=7 patients) caused significant Akt phosphorylation at serine-473, indicating activation of Akt. FPA124 and 10-DEBC were without effects on noradrenaline-, phenylephrine-, or EFS-induced contraction of prostate strips.
Prostate α1-adrenoceptors activate Akt. Consequently, Akt is a target of α1-blocker therapy, which has been unknown to date. Our findings point to functions of prostate α1-adrenoceptors besides contraction.
α1-肾上腺素受体除了在收缩中起作用外，还可能参与前列腺增生。这需要通过促进生长的信号通路来实现受体信号转导。Akt（也称为蛋白激酶 B）是生长和分化的重要调节剂。
研究人前列腺中的α1-肾上腺素受体是否激活 Akt。
从接受根治性前列腺切除术的患者中获得前列腺组织。通过 RT-PCR、Western blot 和免疫组织化学研究 Akt 表达。用磷酸化特异性抗体通过 Western blot 分析评估去甲肾上腺素（30 μM）和苯肾上腺素（10 μM）对 Akt 的激活作用。在肌动描记法测量中研究 Akt 抑制剂 FPA-124 和 10-DEBC 对苯肾上腺素、去甲肾上腺素和电刺激（EFS）诱导的收缩的影响。
通过 RT-PCR 在所有前列腺样本中均检测到所有三种 Akt 同工型（Akt1、Akt2、Akt3）的 mRNA（n=6 例患者）。通过 Western blot 分析证实了蛋白表达（n=8 例患者）。Akt 的免疫组织化学染色显示前列腺平滑肌细胞中存在强烈的免疫反应性（n=5 例患者）。用去甲肾上腺素（30 μM，n=8 例患者）或苯肾上腺素（10 μM，n=7 例患者）刺激前列腺组织会导致 Akt 在丝氨酸 473 处明显磷酸化，表明 Akt 被激活。FPA124 和 10-DEBC 对前列腺带的去甲肾上腺素、苯肾上腺素或 EFS 诱导的收缩没有影响。
前列腺α1-肾上腺素受体激活 Akt。因此，Akt 是α1-阻滞剂治疗的靶点，这是迄今为止未知的。我们的发现指出了前列腺α1-肾上腺素受体除收缩以外的功能。
