Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase
Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase
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DOI：
10.1152/ajplung.00420.2003
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发表时间：
2004-07-01
影响因子：
4.9
通讯作者：
Uhlig, S
中科院分区：
文献类型：
--
作者：
Martin, C;Göggel, R;Uhlig, S
血小板活化因子（PAF）主要通过释放血栓素来收缩气道和血管的平滑肌。平滑肌的收缩被认为是通过肌球蛋白轻链激酶的钙和三磷酸肌醇（IP 3）依赖性激活或通过最近发现的Rho激酶途径介导的。在这里，我们研究了这两种途径的贡献PAF和血栓素受体介导的支气管和血管收缩在两个不同的大鼠模型：离体灌注肺（IPL）和精密切割肺切片。抑制IP 3受体（1-10 μ M xestospongin C）或抑制磷脂酰肌醇特异性PLC（30 μ M L-108）不影响支气管收缩，但减弱PAF引起的持续血管收缩。抑制肌球蛋白轻链激酶（35 μ M ML-7）或钙调蛋白激酶激酶（26 μ M STO 609），调节肌球蛋白轻链的磷酸化，对PAF或血栓素诱导的升压反应只有很小的影响。类似地，抑制钙调蛋白依赖性蛋白的calmidazolium（10 μ M）仅微弱地降低气道反应。与此相反，Y-27632（10 μ M），Rho激酶抑制剂，衰减PAF触发的血栓素释放，并提供部分或完全抑制PAF和血栓素诱导的升压反应，分别。总之，我们的数据表明，PAF和血栓素受体介导的平滑肌收缩在很大程度上取决于Rho激酶途径。
Platelet-activating factor (PAF) contracts smooth muscle of airways and vessels primarily via release of thromboxane. Contraction of smooth muscle is thought to be mediated either by calcium and inositol trisphosphate (IP3)-dependent activation of the myosin light chain kinase or, alternatively, via the recently discovered Rho-kinase pathway. Here we investigated the contribution of these two pathways to PAF and thromboxane receptor-mediated broncho- and vasoconstriction in two different rat models: the isolated perfused lung (IPL) and precision-cut lung slices. Inhibition of the IP3 receptor (1-10 muM xestospongin C) or inhibition of phosphatidylinositol-specific PLC (30 muM L-108) did not affect bronchoconstriction but attenuated the sustained vasoconstriction by PAF. Inhibition of myosin light chain kinase (35 muM ML-7) or of calmodulin kinase kinase (26 muM STO609), which regulates the phosphorylation of the myosin light chain, had only a small effect on PAF- or thromboxane-induced pressor responses. Similarly, calmidazolium (10 muM), which inhibits calmodulin-dependent proteins, only weakly reduced the airway responses. In contrast, Y-27632 (10 muM), a Rho-kinase inhibitor, attenuated the thromboxane release triggered by PAF and provided partial or complete inhibition against PAF- and thromboxane-induced pressor responses, respectively. Together, our data indicate that PAF- and thus thromboxane receptor-mediated smooth muscle contraction depends largely on the Rho-kinase pathway.