Sphingosine 1-phosphate enhances portal pressure in isolated perfused liver via S1P2 with Rho activation.
Sphingosine 1-phosphate enhances portal pressure in isolated perfused liver via S1P2 with Rho activation.
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DOI：
10.1016/j.bbrc.2004.04.207
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发表时间：
2004-07
影响因子：
3.1
通讯作者：
H. Ikeda;K. Nagashima;M. Yanase;T. Tomiya;M. Arai;Y. Inoue;Kazuaki Tejima;Takako Nishikawa;N. Watanabe;M. Omata;K. Fujiwara
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文献类型：
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作者：
H. Ikeda;K. Nagashima;M. Yanase;T. Tomiya;M. Arai;Y. Inoue;Kazuaki Tejima;Takako Nishikawa;N. Watanabe;M. Omata;K. Fujiwara
虽然结构变化是决定门脉高压血管阻力的最重要因素，但血管活性介质也参与了其调节。肝星状细胞（HSC）被认为在调节肝内血管阻力中发挥作用，这是基于它们在Disse空间中的驻留和收缩能力。由于1-磷酸鞘氨醇（S1 P）已被证明可以刺激HSC收缩，我们想知道S1 P是否可以调节门静脉压力。0.5-5μM的S1 P增加离体大鼠灌注肝脏的门静脉压力。在S1 P2的结合拮抗剂JTE-013存在下，该效应被消除。用5μM S1 P灌注离体大鼠肝脏可增加肝脏中Rho活性，与JTE-013共灌注可取消S1 P诱导的Rho激活。由于S1 P在人血浆中的浓度约为0.2μM，因此S1 P在生理和病理状态下很容易调节门静脉血管张力。S1 P2拮抗剂可作为门静脉高压症的治疗药物。
Although structural changes are most important to determine vascular resistance in portal hypertension, vasoactive mediators also contribute to its regulation. Hepatic stellate cells (HSCs) are assumed to play a role in modulating intrahepatic vascular resistance based on their residence in the space of Disse and capacity to contract. Because sphingosine 1-phosphate (S1P) has been shown to stimulate HSC contractility, we wondered if S1P could regulate portal pressure. S1P at 0.5–5μM increased portal pressure in isolated rat perfused liver. This effect was abrogated in the presence of a binding antagonist for S1P2, JTE-013. Perfusion of isolated rat liver with 5μM S1P increased Rho activity in the liver, and co-perfusion with JTE-013 cancelled S1P-induced Rho activation. Because S1P is present in human plasma at approximately 0.2μM, S1P might readily regulate portal vascular tone in physiological and pathological status. The antagonist for S1P2merits consideration for treatment of portal hypertension.