RhoA/Rho kinase-mediated Ca2+ sensitization in the contraction of human prostate

✍ Scribed by Ryosuke Takahashi; Junji Nishimura; Narihito Seki; Takakazu Yunoki; Toshihisa Tomoda; Hideo Kanaide; Seiji Naito

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 198 KB
• Volume: 26
• Category: Article
• ISSN: 0733-2467
• DOI: 10.1002/nau.20365

✦ Synopsis

Abstract

Aims

The contractile mechanisms of prostatic smooth muscle have been extensively investigated at the receptor level. However, the intracellular mechanisms have not yet been fully elucidated, especially in human tissue. In the present study, we examined the functional role of RhoA/Rho kinase (ROCK), one of the major intracellular molecules involved in smooth muscle contraction, in the contraction of the human prostate.

Methods

Ring preparations made of cultured human prostatic stromal cells (CHPSCs) or fresh human prostatic tissue was used for an isometric tension study. Gene transfer using baculovirus vector and α‐toxin permeabilized preparations were also used.

Results

RhoA, ROCK I and ROCK II proteins were all expressed in CHPSCs and fresh human prostatic tissue. In CHPSCs ring preparations, the contraction induced by endothelin (ET)‐1 was enhanced by over‐expression of RhoA and inhibited by ROCK inhibitor. In α‐toxin permeabilized preparations, ET‐1 or GTP‐γS induced an additional contraction at a constant [Ca^2+^]~i~, that was inhibited by ROCK inhibitor. In fresh human prostatic tissue, norepinephrine (NE)‐induced contraction was inhibited by ROCK inhibitor at a constant [Ca^2+^]~i~ in α‐toxin permeabilized preparations.

Conclusions

These results suggested that RhoA/ROCK‐mediated Ca^2+^ sensitization is likely involved in the contraction of the human prostate. The antagonisms of this pathway may thus be useful as an alternative target in the treatment of benign prostatic hyperplasia (BPH). Neurourol. Urodynam. 26:547–551, 2007. © 2007 Wiley‐Liss, Inc.