RT Journal Article
SR Electronic
T1 Intermediate-Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channel, K<sub>Ca</sub>3.1, as a Novel Therapeutic Target for Benign Prostatic Hyperplasia
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 528
OP 536
DO 10.1124/jpet.111.182782
VO 338
IS 2
A1 Susumu Ohya
A1 Satomi Niwa
A1 Yoshiyuki Kojima
A1 Shoichi Sasaki
A1 Motomu Sakuragi
A1 Kenjiro Kohri
A1 Yuji Imaizumi
YR 2011
UL http://jpet.aspetjournals.org/content/338/2/528.abstract
AB Recently, a new experimental stromal hyperplasia animal model corresponding to clinical benign prostatic hyperplasia (BPH) was established. The main objective of this study was to elucidate the roles of the intermediate-conductance Ca2+-activated K+ channel (KCa3.1) in the implanted urogenital sinus (UGS) of stromal hyperplasia BPH model rats. Using DNA microarray, real-time polymerase chain reaction, Western blot, and/or immunohistochemical analyses, we identified the expression of KCa3.1 and its transcriptional regulators in implanted UGS of BPH model rats and prostate needle-biopsy samples and surgical prostate specimens of BPH patients. We also examined the in vivo effects of a KCa3.1 blocker, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), on the proliferation index of implanted UGS by measurement of UGS weights and proliferating cell nuclear antigen immunostaining. KCa3.1 genes and proteins were highly expressed in implanted UGS rather than in the normal host prostate. In the implanted UGS, the gene expressions of two transcriptional regulators of KCa3.1, repressor element 1-silencing transcription factor and c-Jun, were significantly down- and up-regulated, and the regulations were correlated negatively or positively with KCa3.1 expression, respectively. Positive signals of KCa3.1 proteins were detected exclusively in stromal cells, whereas they were scarcely immunolocalized to basal cells of the epithelium in implanted UGS. In vivo treatment with TRAM-34 significantly suppressed the increase in implanted UGS weights compared with the decrease in stromal cell components. Moreover, significant levels of KCa3.1 expression were observed in human BPH samples. KCa3.1 blockers may be a novel treatment option for patients suffering from BPH.