Takahashi Ryosuke, Nishimura Junji, Seki Narihito, Yunoki Takakazu, Tomoda Toshihisa, Kanaide Hideo, Naito Seiji
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Neurourol Urodyn. 2007;26(4):547-551. doi: 10.1002/nau.20365.
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.
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 alpha-toxin permeabilized preparations were also used.
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 alpha-toxin permeabilized preparations, ET-1 or GTP-gammaS 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 alpha-toxin permeabilized preparations.
These 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).
前列腺平滑肌的收缩机制已在受体水平上得到广泛研究。然而，细胞内机制尚未完全阐明，尤其是在人体组织中。在本研究中，我们研究了RhoA/ Rho激酶（ROCK）这一参与平滑肌收缩的主要细胞内分子之一在人前列腺收缩中的功能作用。
使用由培养的人前列腺基质细胞（CHPSC）或新鲜人前列腺组织制成的环形标本进行等长张力研究。还使用了杆状病毒载体基因转移和α-毒素通透标本。
RhoA、ROCK I和ROCK II蛋白均在CHPSC和新鲜人前列腺组织中表达。在CHPSC环形标本中，内皮素（ET）-1诱导的收缩通过RhoA的过表达而增强，并被ROCK抑制剂抑制。在α-毒素通透标本中，ET-1或GTP-γS在恒定的[Ca2+]i水平诱导额外的收缩，这被ROCK抑制剂抑制。在新鲜人前列腺组织中，在α-毒素通透标本中，去甲肾上腺素（NE）诱导的收缩在恒定的[Ca2+]i水平被ROCK抑制剂抑制。
这些结果表明，RhoA/ROCK介导的Ca2+致敏可能参与人前列腺的收缩。因此，该途径的拮抗剂可能作为治疗良性前列腺增生（BPH）的替代靶点。
