Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.
Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.
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发表时间：
1995-10
影响因子：
3.6
通讯作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
中科院分区：
文献类型：
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作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
血管紧张素II （ANG II）受体（AT1）是肾素-血管紧张素系统的核心组成部分；因此，调节其表达可能对心血管反应性很重要。我们证明ANG II在大鼠主动脉血管平滑肌细胞中下调其受体。100 nM ANG II孵育4小时后，AT1 mRNA和蛋白含量分别降低70%和35%。这种同源下调是浓度和时间依赖性的，并被AT1拮抗剂氯沙坦阻断。它似乎不是由蛋白激酶C或其他蛋白激酶介导的，而是依赖于对氧化苯larsin敏感的持续信号通路。受体激动剂-凝血酶、ATP和camp增加剂福斯克林均可观察到异源下调。ANG II抑制50%的转录并破坏AT1 mRNA的稳定性。AT1 mRNA的下调被转录和翻译抑制剂阻断，这表明它需要一个或多个蛋白因子的表达。这些结果表明，ANG II通过转录和转录后机制下调其血管受体。AT1受体的同源和异源下调可能参与血管张力对血管活性激素的协调生理适应。
The vascular angiotensin II (ANG II) receptor (AT1) is a central component of the renin-angiotensin system; thus, regulation of its expression is likely to be important in cardiovascular responsiveness. We demonstrate that ANG II down-regulates its receptor in rat aortic vascular smooth muscle cells. Incubation for 4 hr with 100 nM ANG II decreased AT1 mRNA and protein by 70% and 35%, respectively. This homologous down-regulation was concentration and time dependent and was blocked by the AT1 antagonist losartan. It did not appear to be mediated by protein kinase C or other protein kinases but was dependent on the sustained signaling pathway sensitive to phenylarsine oxide. Heterologous down-regulation was observed with the agonists alpha-thrombin and ATP and the cAMP-increasing agent forskolin. ANG II inhibited transcription by 50% and destabilized the AT1 mRNA. Down-regulation of AT1 mRNA was blocked by transcription and translation inhibitors, suggesting that it required expression of a protein factor or factors. These results indicate that ANG II down-regulates its vascular receptor by both transcriptional and post-transcriptional mechanisms. Homologous and heterologous down-regulation of the AT1 receptor may participate in the coordinated physiological adaptation of vascular tone to vasoactive hormones.