Ardaillou R
Institut National de la Santé et de la Recherche Médicale, Unit 489, Hôpital Tenon, Paris, France.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S30-9.
This review examines the recent progress in the field of angiotensin receptors. Multiplicity of these receptors was demonstrated initially on the basis of pharmacologic differences and then confirmed by expression cloning. AT1 receptors are predominant in the adult. They are widely distributed and mediate all of the known biologic effects of angiotensin II (AngII) through a variety of signal transduction systems, including activation of phospholipases C and A2, inhibition of adenylate cyclase, opening of calcium channels, and activation of tyrosine kinases. AT2 receptors are predominant in the fetus, but also present in adult tissues such as the adrenals, ovaries, uterus, and brain. AngII via these receptors exerts effects often opposed to those mediated by the AT1 receptors. Signal transduction implicates protein tyrosine phosphatase stimulation. AT1 and AT2 receptor expressions are regulated differently, and regulation is also tissue-specific. AT1 and AT2 receptors have been demonstrated in endothelial cells. Activation of AT1 receptors results in production of vasodilatory agents, nitric oxide, and prostacyclin (PGI2), which counteract the direct vasoconstrictor effects of Ang II on the adjacent smooth muscle cells. AT1 receptors on mesangial cells, smooth muscle cells, and fibroblasts are involved in cell growth and fibrosis, the latter being due both to an increase in the synthesis and a decrease in the degradation of the main components of the extracellular matrix. These AT1 receptor-dependent effects are for the most part indirect and mediated by growth factors, cytokines, and other peptides, including endothelin, transforming growth factor-beta1, and platelet-derived growth factor. AngII is metabolized into active fragments by deletion of the terminal amino acids on both ends. AngIII and AngIV are formed by successive deletions of aspartic acid and arginine at the N terminus. AngII (1-7) is obtained by deletion of phenylalanine at the C terminus. AngIII shares the same receptors and exerts the same effects as AngII. AngIV and AngII (1-7) recognize the AT1 and AT2 receptors with a lesser affinity than AngII and, in addition, possess their own receptors that mediate effects often opposed to those of AngII.
本综述探讨了血管紧张素受体领域的最新进展。这些受体的多样性最初是基于药理学差异得以证实，随后通过表达克隆得到确认。AT1受体在成体中占主导地位。它们广泛分布，并通过多种信号转导系统介导血管紧张素II（AngII）的所有已知生物学效应，包括激活磷脂酶C和A2、抑制腺苷酸环化酶、开放钙通道以及激活酪氨酸激酶。AT2受体在胎儿中占主导地位，但也存在于肾上腺、卵巢、子宫和脑等成体组织中。AngII通过这些受体发挥的作用通常与AT1受体介导的作用相反。信号转导涉及蛋白酪氨酸磷酸酶的刺激。AT1和AT2受体的表达受到不同的调节，且这种调节也具有组织特异性。在内皮细胞中已证实存在AT1和AT2受体。激活AT1受体可导致血管舒张剂、一氧化氮和前列环素（PGI2）的产生，这些物质可抵消Ang II对相邻平滑肌细胞的直接血管收缩作用。系膜细胞、平滑肌细胞和成纤维细胞上的AT1受体参与细胞生长和纤维化，后者是由于细胞外基质主要成分的合成增加和降解减少所致。这些依赖于AT1受体的效应在很大程度上是间接的，由生长因子、细胞因子和其他肽介导，包括内皮素、转化生长因子-β1和血小板衍生生长因子。AngII通过两端末端氨基酸的缺失代谢为活性片段。AngIII和AngIV分别通过N端天冬氨酸和精氨酸的连续缺失形成。AngII（1-7）通过C端苯丙氨酸的缺失获得。AngIII与AngII具有相同的受体并发挥相同的作用。AngIV和AngII（1-7）与AT1和AT2受体的亲和力低于AngII，此外，它们还拥有自身的受体，介导的效应通常与AngII相反。
