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Obstruction enhances rho-kinase pathway and diminishes protein kinase C pathway in carbachol-induced calcium sensitization in contraction of α-toxin permeabilized guinea pig detrusor smooth muscle.

Abstract：

AIMS:We investigated the relative important role of rho kinase (ROK) and protein kinase C (PKC) pathways in carbachol (CCh)-induced Ca(2+) sensitization in α-toxin permeabilized Guinea pig detrusor smooth muscle (DSM) following bladder outlet obstruction (BOO). METHODS:Bladder outlet obstruction was created by placement of a silver jeweler's jump rings loosely round the urethro-vesical junction of Guinea pigs. Sham operated Guinea pig underwent a similar protocol without application of the ring and served as control. α-Toxin permeabilized DSM strips from control Guinea pigs and those subjected to 6-8 weeks of BOO were mounted horizontally for isometric force recording in 100 µl relaxing solution on perspex block. The effect of ROK inhibitor (Y-27632) and PKC inhibitor (GF-109203X) on CCh-induced Ca(2+) sensitization was studied during sustained contraction. Permeabilized DSM strips were also stimulated by cumulative increase of Ca(2+) concentration compared to that in control in the presence and in the absence of sensitization-induced PKC activator, phorbol 12,13-dibutyrate. RESULTS:Ca(2+) sensitization-induced by CCh was greater in BOO compared to controls. This muscarinic agonist-induced Ca(2+) sensitization was inhibited by Y-27632 or GF-109203X. The inhibitory effect of Y-27632 (5 µM) was greater while the inhibitory effect of GF-109203X (5 µM) was smaller in BOO compared to that in controls. Phorbol 12,13-dibutyrate (1 µM) markedly increased Ca(2+) sensitivity in controls but not in BOO. CONCLUSIONS:Our findings provide the first evidence that BOO enhances the ROK pathway and diminishes the PKC pathway in CCh-induced Ca(2+) sensitization in contraction of permeabilized Guinea pig DSM and suggest that inhibitors of ROK might potentially relieve bladder dysfunction related to BOO.

journal_name

Neurourol Urodyn

journal_title

Neurourology and urodynamics

authors

Shahab N,Kajioka S,Takahashi-Yanaga F,Onimaru M,Matsuda M,Seki N,Naito S

doi

10.1002/nau.21193

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

593-9

issue

eissn

0733-2467

issn

1520-6777

journal_volume

pub_type

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Obstruction enhances rho-kinase pathway and diminishes protein kinase C pathway in carbachol-induced calcium sensitization in contraction of α-toxin permeabilized guinea pig detrusor smooth muscle.