Sphingosine-1-phosphate induced contraction of bladder smooth muscle.
Sphingosine-1-phosphate induced contraction of bladder smooth muscle.
复制标题
1-磷酸鞘氨醇诱导膀胱平滑肌收缩。
DOI：
10.1016/j.ejphar.2013.10.004
复制
发表时间：
2013
影响因子：
5
通讯作者：
Moreland,RobertS
中科院分区：
文献类型：
--
作者：
Kendig,DerekM;Matsumoto,AlecK;Moreland,RobertS
鞘氨醇-1-磷酸（S1 P）是一种具有生物活性的鞘脂，可收缩大多数平滑肌。尽管S1 P已显示收缩膀胱平滑肌，但S1 P启动收缩的机制尚未得到广泛研究。本研究的目的是确定S1 P诱导的力产生和肌球蛋白轻链（MLC）磷酸化是否依赖于蛋白激酶C（PKC）和Rho激酶（ROCK）介导的钙致敏途径，以及S1 P受体在这种反应中的重要性。固定家兔和大鼠膀胱平滑肌条，记录等长收缩力，并在存在和不存在PKC（3 µM双吲哚马来酰亚胺-1）或ROCK（1 µM H-1172）抑制剂的情况下，对卡巴胆碱或S1 P进行收缩反应。10 µM S1 P产生的力约为兔膀胱平滑肌对110 mM KCl反应产生的力的40%。高达100 µM的S1 P在大鼠膀胱平滑肌中未产生反应，诱发的任何反应均归因于溶剂（NaOH）。S1 P依赖性力的发展与Ser 19的伴随增加有关，但与双Thr 18/Ser 19 MLC磷酸化无关。抑制PKC降低力的发展，而抑制ROCK废除S1 P诱导的力。S1 P2受体的抑制剂JTE-013，放松了S1 P诱导的收缩;而，与S1 P2受体，二氢-S1 P，具有低亲和力的激动剂，不引起收缩。我们的研究结果表明，S1 P合同兔，而不是大鼠，膀胱平滑肌通过S1 P2受体，是依赖于MLC磷酸化和肌丝钙敏化主要响应于ROCK激活。
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most smooth muscles. Although S1P has been shown to contract bladder smooth muscle, the mechanism(s) by which S1P initiates contraction has not been extensively investigated. The goal of this study was to determine if S1P-induced force generation and myosin light chain (MLC) phosphorylation are dependent on calcium sensitization pathways mediated by protein kinase C (PKC) and Rho kinase (ROCK) and which S1P receptor is important in this response. Bladder smooth muscle strips from rabbit and rat were mounted for isometric force recording and contracted in response to carbachol or S1P in the presence and absence of an inhibitor of PKC (3 µM Bisindolylmaleimide-1) or ROCK (1 µM H-1172). 10 µM S1P produced approximately 40% of the force generated in response to 110 mM KCl in rabbit bladder smooth muscle. S1P, up to 100 µM, did not produce a response in rat bladder smooth muscle, any response evoked was due to solvent (NaOH). S1P-dependent force development was associated with a concomitant increase in Ser19, but not dual Thr18/Ser19MLC phosphorylation. Inhibition of PKC decreased force development, whereas inhibition of ROCK abolished S1P-induced force. An inhibitor of the S1P2 receptor, JTE-013, relaxed a S1P-induced contraction; whereas, an agonist with low affinity to the S1P2 receptor, dihydro-S1P, did not elicit a contraction. Our results suggest that S1P contracts rabbit, but not rat, bladder smooth muscle via the S1P2 receptor and is dependent on MLC phosphorylation and myofilament calcium sensitization primarily in response to ROCK activation.