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

Neurourology and Urodynamics - Tập 26 Số 4 - Trang 547-551 - 2007
Ryosuke Takahashi1, Junji Nishimura2, Narihito Seki1, Takakazu Yunoki1, Toshihisa Tomoda1, Hideo Kanaide2, Seiji Naito1
1Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Tóm tắt

AbstractAimsThe 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.MethodsRing 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.ResultsRhoA, 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 [Ca2+]i, that was inhibited by ROCK inhibitor. In fresh human prostatic tissue, norepinephrine (NE)‐induced contraction was inhibited by ROCK inhibitor at a constant [Ca2+]i in α‐toxin permeabilized preparations.ConclusionsThese results suggested that RhoA/ROCK‐mediated Ca2+ 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.

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Neurourology and Urodynamics

Tập 26 Số 4

547-551

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