The cAMP effector EPAC activates Elk1 transcription factor in prostate smooth muscle, and is a minor regulator of α1-adrenergic contraction

Journal of Biomedical Science

Research

Henning Schmetkamp¹  Christian G Stief¹  Beata Rutz¹  Sebastian Walther¹  Martin Hennenberg¹  Christian Gratzke¹  Frank Strittmatter¹ 

[1] Department of Urology, Ludwig-Maximilians University, Munich, Germany;

关键词: α1-adrenoceptor;    Smooth muscle contraction;    Smooth muscle relaxation;    Cyclic adenosin-3,5-monophosphate;    EPAC;    Elk1;    Benign prostate hyperplasia (BPH);    Benign prostate obstruction (BPO);    Bladder outlet obstruction (BOO);    Lower urinary tract symptoms (LUTS);   

DOI  :  10.1186/1423-0127-20-46

 received in 2013-04-03, accepted in 2013-06-19,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundProstate smooth muscle tone is regulated by α1-adrenoceptor-induced contraction and cAMP-mediated relaxation. EPAC is an effector of cAMP, being involved in smooth muscle relaxation and cell cycle control outside the lower urinary tract. Here, we investigated the expression and function of EPAC in human prostate tissues from patients undergoing radical prostatectomy.ResultsmRNA and protein expression of EPAC was detected in all prostate tissues by RT-PCR and Western blot analysis. Immunoreactivity was observed in stromal cells, and colocalized with immunofluorescence for α-smooth muscle actin and calponin. Under normal conditions, noradrenaline- or phenylephrine-induced contraction of prostate strips in the organ bath was not affected by the EPAC activator pCPT (SP-8-pCPT-2′-O-Me-cAMPS.NA) (30 μM). However, when the cyclooxygenase inhibitor indomethacin (50 μM) was added, EPAC activators pCPT and OME (8-CPT-2′-O-Me-cAMP.Na) (30 μM) significantly reduced contractions by low concentrations of phenylephrine. These effects were not observed on noradrenaline-induced contraction. OME and pCPT caused phosphorylation of the transcription factor Elk1 in prostate tissues. Elk1 activation was confirmed by EMSA (electrophoretic mobility shift assay), where OME and pCPT incresed Elk1 binding to a specific DNA probe.ConclusionsEPAC activation may reduce α1-adrenergic prostate contraction in the human prostate, although this effect is masked by cyclooxygenases and β-adrenoceptors. A main EPAC function in the human prostate may be the regulation of the transcription factor Elk1.

【 授权许可】

Unknown   
© Hennenberg et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.