International union of pharmacology. XXIII. The angiotensin II receptors.
International union of pharmacology. XXIII. The angiotensin II receptors.
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DOI：
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发表时间：
2000-09
影响因子：
21.1
通讯作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger
中科院分区：
文献类型：
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作者：
M. Gasparo;K. Catt;T. Inagami;J. Wright;T. Unger
血管紧张素II（AngII）的心血管和其他作用是由AT（1）和AT（2）受体介导的，AT（1）和AT（2）受体是7种跨膜糖蛋白，具有30%的序列相似性。大多数物种表达一个常染色体AT（1）基因，但两个相关的AT（1A）和AT（1B）受体基因在啮齿类动物中表达。AT（1）受体主要与G（q/11）偶联，并通过磷脂酶A、C、D、肌醇磷酸、钙通道和各种丝氨酸/苏氨酸和酪氨酸激酶发出信号。许多AT（1）诱导的生长反应是由生长因子受体的反式激活介导的。激动剂和非肽拮抗剂配体的受体结合位点已被确定。后一种化合物在心血管疾病中与血管紧张素转化酶抑制剂一样有效，但耐受性更好。AT（2）受体在胎儿发育期间以高密度表达。它在成人组织中的丰度要低得多，并且在病理条件下上调。其信号通路包括丝氨酸和酪氨酸磷酸酶、磷脂酶A（2）、一氧化氮和环磷酸鸟苷。AT（2）受体抵消AT（1）和生长因子受体引发的几种生长反应。AT（4）受体特异性结合Ang IV（Ang 3-8），并且位于脑和肾中。其信号传导机制尚不清楚，但它会影响局部血流，并与认知过程、感觉和运动功能有关。虽然AT（1）受体介导Ang II的大多数已知作用，但AT（2）受体有助于调节血压和肾功能。特异性非肽类受体拮抗剂的开发使肾素-血管紧张素系统的生理学、药理学和治疗取得了重大进展。
The cardiovascular and other actions of angiotensin II (Ang II) are mediated by AT(1) and AT(2) receptors, which are seven transmembrane glycoproteins with 30% sequence similarity. Most species express a single autosomal AT(1) gene, but two related AT(1A) and AT(1B) receptor genes are expressed in rodents. AT(1) receptors are predominantly coupled to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. Many AT(1)-induced growth responses are mediated by transactivation of growth factor receptors. The receptor binding sites for agonist and nonpeptide antagonist ligands have been defined. The latter compounds are as effective as angiotensin converting enzyme inhibitors in cardiovascular diseases but are better tolerated. The AT(2) receptor is expressed at high density during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signaling pathways include serine and tyrosine phosphatases, phospholipase A(2), nitric oxide, and cyclic guanosine monophosphate. The AT(2) receptor counteracts several of the growth responses initiated by the AT(1) and growth factor receptors. The AT(4) receptor specifically binds Ang IV (Ang 3-8), and is located in brain and kidney. Its signaling mechanisms are unknown, but it influences local blood flow and is associated with cognitive processes and sensory and motor functions. Although AT(1) receptors mediate most of the known actions of Ang II, the AT(2) receptor contributes to the regulation of blood pressure and renal function. The development of specific nonpeptide receptor antagonists has led to major advances in the physiology, pharmacology, and therapy of the renin-angiotensin system.