血管紧张素II刺激的血管平滑肌细胞中的次级信号传导机制。

Secondary signalling mechanisms in angiotensin II-stimulated vascular smooth muscle cells.

Griendling K K, Berk B C, Socorro L, Tsuda T, Delafontaine P, Alexander R W

Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Clin Exp Pharmacol Physiol. 1988 Feb;15(2):105-12. doi: 10.1111/j.1440-1681.1988.tb01051.x.

Abstract

Activation of vascular smooth muscle by angiotensin II results in the generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). 2. IP3 is responsible for mobilizing calcium from endoplasmic reticulum. This signal is transient, most likely serving to initiate calcium events leading to contraction, and is attenuated by activation of protein kinase C. 3. DG stimulates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. Accumulation of DG/activation of protein kinase C is sustained, and may be enhanced by concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. 4. Angiotensin II-stimulated, phospholipase C-mediated IP3 formation is also modulated by a pertussis toxin-insensitive guanine nucleotide regulatory protein. 5. The GTP binding protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle cells to angiotensin II stimulation.

摘要

血管紧张素II激活血管平滑肌会产生两种第二信使，即三磷酸肌醇（IP3）和二酰甘油（DG）。2. IP3负责从内质网中动员钙。该信号是短暂的，很可能用于启动导致收缩的钙事件，并通过蛋白激酶C的激活而减弱。3. DG刺激蛋白激酶C并最终刺激Na+/H+交换，导致细胞内碱化。DG的积累/蛋白激酶C的激活是持续的，并且可能通过同时发生的细胞内碱化而增强。持续反应诱导的延迟似乎与血管紧张素II受体复合物的细胞处理有关。4. 血管紧张素II刺激的、磷脂酶C介导的IP3形成也受到一种对百日咳毒素不敏感的鸟嘌呤核苷酸调节蛋白的调节。5. GTP结合蛋白、受体-配体复合物的移动以及两种第二信使IP3和DG产生的信号以复杂的方式相互作用，从而引起血管平滑肌细胞对血管紧张素II刺激的综合反应。