Bauer Ricarda M, Strittmatter Frank, Gratzke Christian, Göttinger Johanna, Schlenker Boris, Reich Oliver, Stief Christian G, Hedlund Petter, Andersson Karl-Erik, Hennenberg Martin
Department of Urology, University of Munich, Germany.
Urol Int. 2011;86(4):427-33. doi: 10.1159/000322639. Epub 2011 Feb 3.
α1-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α1-adrenoceptor functions besides contraction. Here, we investigated whether α1-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2).
Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments.
Stimulation of human prostate tissue with noradrenaline (30 μM) or phenylephrine (10 μM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 μM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126.
α1-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α1-adrenoceptors in the regulation of prostate growth.
α1肾上腺素能受体被认为对前列腺平滑肌张力的调节至关重要。然而,先前的研究表明α1肾上腺素能受体除了收缩作用外还有其他功能。在此,我们研究了人前列腺中的α1肾上腺素能受体是否能激活细胞外信号调节激酶(ERK1/2)。
对接受根治性前列腺切除术患者的前列腺组织进行体外刺激。通过蛋白质印迹分析评估ERK1/2的激活情况。通过免疫组织化学研究ERK1/2的表达。在器官浴实验中研究U0126抑制ERK1/2对去氧肾上腺素诱导的收缩的影响。
用去甲肾上腺素(30μM)或去氧肾上腺素(10μM)刺激人前列腺组织导致ERK激活。这表现为磷酸化ERK1/2水平升高。在平滑肌细胞中观察到前列腺中ERK1/2的表达。用U0126(30μM)孵育人前列腺组织导致ERK1/2受到抑制。U0126未调节去氧肾上腺素诱导的前列腺组织剂量依赖性收缩。
人前列腺中的α1肾上腺素能受体与ERK1/2偶联。这可能部分解释了先前表明α1肾上腺素能受体在前列腺生长调节中起作用的观察结果。