- 作者：Frank Strittmatter ; Sebastian Walther ; Alexander Roosen ; Beata Rutz ; Boris Schlenker ; Sebastian Limmer ; Raphaela Waidelich ; Christian G. Stief ; Christian Gratzke ; christian.gratzke@med.uni-muenchen.de ; Martin Hennenberg
- 关键词：Prostate hyperplasia ; Lower urinary tract symptoms (LUTS) ; 伪1-Adrenoceptor ; Protein kinase B/Akt ; Smooth muscle ; Contraction
- 刊名：Life Sciences
- 出版年：2012
- 期刊代码：62_00243205
- 类别：imm
- 出版时间：10 March, 2012
- 卷：90
- 期：11-12
- 页码：446-453
- 文件大小：904 K
Aims
Besides their role in contraction, 伪1-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. Objective: To investigate whether 伪1-adrenoceptors in the human prostate activate Akt.Main methods
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 渭M) and phenylephrine (10 渭M) 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.
Key findings
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 渭M, n = 8 patients) or phenylephrine (10 渭M, 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.
Significance
Prostate 伪1-adrenoceptors activate Akt. Consequently, Akt is a target of 伪1-blocker therapy, which has been unknown to date. Our findings point to functions of prostate 伪1-adrenoceptors besides contraction.