Abstract
Background: Prostate smooth muscle contraction plays an important role for pathophysiology and treatment of male lower urinary tract symptoms (LUTS) but is incompletely understood. Because the efficacy of available medication is limited, novel options and improved understanding of prostate smooth muscle contraction are of high demand. Recently, a possible role of polo-like kinase 1 (PLK1) has been suggested for smooth muscle contraction outside the lower urinary tract. Here, we examined effects of PLK inhibitors on contraction of human prostate tissue.Methods: Prostate tissues were obtained from radical prostatectomy. RT-PCR, Western blot and immunofluorescence were performed to detect PLK expression and phosphorylated PLK. Smooth muscle contractions were induced by electric field stimulation (EFS), α1-agonists, endothelin-1, or the thromboxane A2 analog U46619 in organ bath.Results: RT-PCR, Western blot, and immunofluorescence suggested expression of PLK1 in the human prostate, which may be located and active in smooth muscle cells. EFS-induced contractions of prostate strips were reduced by SBE 13 (1 μM), cyclapolin 9 (3 μM), TAK 960 (100 nM), and Ro 3280 (100 nM). SBE 13 and cyclapolin 9 inhibited contractions by the α1-agonists methoxamine, phenylephrine, and noradrenaline. In contrast, no effects of SBE 13 or cyclapolin 9 on endothelin-1- or U46619-induced contractions were observed.Conclusion: Alpha1-adrenergic smooth muscle contraction in the human prostate can be inhibited by PLK inhibitors. PLK-dependent signaling may be a new pathway, which promotes α1-adrenergic contraction of prostate smooth muscle cells. As contractions by endothelin and U46619 are not susceptible to PLK inhibition, this reflects divergent regulation of adrenergic and non-adrenergic prostate smooth muscle contraction.
Highlights
Male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) are commonly caused by bladder outlet obstruction (BOO), which is driven by increased prostate smooth muscle tone and prostate growth (Caine et al, 1976; Hennenberg et al, 2014)
As a role in smooth muscle contraction may only be supposed for polo-like kinase 1 (PLK1), Western blot analysis was performed for PLK1
Following semiquantitative evaluation of bands, correlation analysis was performed for PLK1 and prostatespecific antigen (PSA)
Summary
Male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) are commonly caused by bladder outlet obstruction (BOO), which is driven by increased prostate smooth muscle tone and prostate growth (Caine et al, 1976; Hennenberg et al, 2014). The most important option are α1-adrenoceptor antagonists, as they may reduce symptoms by inhibition of α1-adrenergic prostate smooth muscle contraction and subsequent improvement of urethral obstruction and bladder emptying (Caine et al, 1976; Oelke et al, 2013; Hennenberg et al, 2014). This concept has been recently challenged, when it became increasingly obvious, that much more signaling pathways may be involved in promotion of prostate smooth muscle contraction (Hennenberg et al, 2014) These may include several GTPases and kinases, as smooth muscle contraction of the human prostate was inhibited by inhibitors for RacGTPases, focal adhesion kinases, p21-activated kinases, and src family kinases (Kunit et al, 2014; Wang et al, 2015, 2016a,b). We examined effects of PLK inhibitors on contraction of human prostate tissue
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