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- W1966552775 abstract "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. Neurourol. Urodynam. 31:593–599, 2012. © 2012 Wiley Periodicals, Inc." @default.
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- W1966552775 date "2012-03-06" @default.
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- W1966552775 title "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" @default.
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- W1966552775 doi "https://doi.org/10.1002/nau.21193" @default.
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