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Obstruction alters muscarinic receptor‐coupled RhoA/Rho‐kinase pathway in the urinary bladder of the rat
Author(s) -
Takahashi Norio,
Shiomi Homare,
Kushida Nobuhiro,
Liu Fei,
Ishibashi Kei,
Yanagida Tomohiko,
Shishido Keiichi,
Aikawa Ken,
Yamaguchi Osamu
Publication year - 2009
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20625
Subject(s) - carbachol , rhoa , endocrinology , contraction (grammar) , detrusor muscle , medicine , muscarinic acetylcholine receptor , rho associated protein kinase , muscle contraction , urinary bladder , bladder outlet obstruction , stimulation , receptor , signal transduction , biology , microbiology and biotechnology , prostate , cancer
Aims The present study investigated the effects of the bladder outlet obstruction (BOO) on the muscarinic receptor (MR)‐coupled RhoA/Rho‐kinase (ROK) pathway in the detrusor smooth muscle of the rat. Methods Detrusor muscle samples were obtained from bladders after 4 weeks of BOO and also from sham‐operated control rats. Contractile responses to electrical field stimulation (EFS) and 1 μM carbachol (Cch) were determined in isolated detrusor strips. The effects of the ROK inhibitor Y‐27632 on the Cch‐induced phasic and sustained contractions were evaluated. Western blotting was used to determine the relative levels of RhoA expression and ROK isoform expression. Results Bladder weight increased significantly after 4 weeks of BOO. Contractile responses to EFS decreased significantly in detrusor muscle from the obstructed bladder. Cch (1 μM) induced a biphasic response consisting of an initial phasic contraction followed by a sustained contraction. Y‐27632 attenuated the phasic and sustained contractions induced by Cch in both control and obstructed bladders. However, BOO caused a significant increase in contractile force during the sustained phase of the contractions induced by Cch. An inhibitory effect of Y‐27632 on the sustained responses to Cch was significantly enhanced in the obstructed bladder. In accordance with the functional study, the expression of RhoA and ROK isoforms (both α and β) at the protein level significantly increased in the obstructed bladder. Conclusions These results suggest that the enhanced MR‐coupled RhoA/ROK pathway contributes to the maintenance of contractile force in the obstructed bladder, as a compensatory mechanism for expelling the urine against the obstruction. Neurourol. Urodynam. 28:257–262, 2009. © 2009 Wiley‐Liss, Inc.