Obstruction enhances rho-kinase pathway and diminishes protein kin-ase C pathway in carbachol-induced calcium sensitization in contraction of α-toxin permeabilized guinea pig detrusor smooth muscle
Obstruction enhances rho-kinase pathway and diminishes protein kin-ase C pathway in carbachol-induced calcium sensitization in contraction of α-toxin permeabilized guinea pig detrusor smooth muscle
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在α-毒素透化豚鼠逼尿肌平滑肌收缩过程中，卡巴胆碱诱导的钙敏化中，阻塞增强了rho激酶途径并减少了蛋白激酶C途径
DOI：
10.1002/nau.21193
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
et.al.
中科院分区：
文献类型：
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作者：
Shahab N;et.al.
目的研究rho激酶（ROK）和蛋白激酶C（PKC）通路在卡巴胆碱（CCh）诱导的α毒素透化豚鼠逼尿肌平滑肌（DSM）Ca 2+增敏中的相对重要作用。假手术豚鼠在不应用环的情况下经历类似的方案，并作为对照。将来自对照豚鼠和经历6-8周BOO的豚鼠的α-毒素透化DSM条水平安装，用于在有机玻璃块上的100 μl松弛溶液中进行等长力记录。在持续收缩过程中研究了ROK抑制剂（Y-27632）和PKC抑制剂（GF-109203 X）对CCh诱导的Ca 2+敏化的影响。在存在和不存在致敏诱导的PKC激活剂佛波醇12，13-二丁酸酯的情况下，与对照组相比，通过Ca 2+浓度的累积增加来刺激透性DSM条。Y-27632或GF-109203 X可抑制毒蕈碱激动剂诱导的Ca 2+致敏作用。与对照组相比，Y-27632（5 µM）的抑制作用更大，而GF-109203 X（5 µM）的抑制作用更小。佛波醇12，13-二丁酸酯（1 µM）显着增加Ca 2+敏感性在控制，但不是在BOO.ConclusionsOur研究结果提供了第一个证据，BOO增强ROK途径，减少PKC途径CCh诱导的Ca 2+敏感性在收缩透化豚鼠DSM，并表明，抑制剂的ROK可能会缓解膀胱功能障碍BOO相关。Neurorol。Urodynam。31：593-599，2012.© 2012 Wiley Periodicals，Inc.
AimsWe investigated the relative important role of rho kinase (ROK) and protein kinase C (PKC) pathways in carbachol (CCh)‐induced Ca2+sensitization in α‐toxin permeabilized Guinea pig detrusor smooth muscle (DSM) following bladder outlet obstruction (BOO).MethodsBladder 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 Ca2+sensitization was studied during sustained contraction. Permeabilized DSM strips were also stimulated by cumulative increase of Ca2+concentration compared to that in control in the presence and in the absence of sensitization‐induced PKC activator, phorbol 12,13‐dibutyrate.ResultsCa2+sensitization‐induced by CCh was greater in BOO compared to controls. This muscarinic agonist‐induced Ca2+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 Ca2+sensitivity in controls but not in BOO.ConclusionsOur findings provide the first evidence that BOO enhances the ROK pathway and diminishes the PKC pathway in CCh‐induced Ca2+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.