BACKGROUND - Little is known about β3 -adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of β-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective β-AR subtype agonist was most involved in the relaxation of isolated human prostate strips.
METHODS - Messenger RNA (mRNA) expression for β1 -, β2 -, and β3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of β-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions.
RESULTS - We confirmed the presence of mRNA for β1 -, β2 -, and β3 -ARs both in normal prostate and in BPH tissues. For β3 -AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in β1 - and β2 -AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different β-AR subtypes. Staining of β3 -AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective β-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective β-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions.
CONCLUSIONS - β3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by β1 - and β3 -AR stimulation. β3 -AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction. Prostate 76:163-171, 2016. © 2015 Wiley Periodicals, Inc.
The Prostate. 2015 Oct 07 [Epub]
Takahisa Suzuki, Atsushi Otsuka, Rikiya Matsumoto, Hiroshi Furuse, Seiichiro Ozono
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. , Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. , Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. , Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. , Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.