Physiological and pharmacological implications of AT1 versus AT2 receptors
Physiological and pharmacological implications of AT1 versus AT2 receptors
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DOI：
10.1046/j.1523-1755.1998.06719.x
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发表时间：
1998-09-01
影响因子：
19.6
通讯作者：
Unger, T
中科院分区：
文献类型：
--
作者：
Chung, O;Kühl, H;Unger, T
血管紧张素II（Ang II）具有多种生理作用，例如，导致细胞外容积和外周血管阻力和血压的增加，并且它还涉及细胞生长和分化的调节。分子克隆和药理学研究已经确定了两大类Ang II受体，命名为AT和AT（2）。血管紧张素II的大部分作用是由AT（1）受体介导的。关于AT（1）受体的生理作用，我们知道的还少得多。最近的证据表明，AT（2）受体参与发育，细胞分化，细胞凋亡和再生的各种组织。AT（1）和AT（2）受体对细胞生长和分化、血管紧张度和精氨酸加压素的释放具有对抗作用。在每种情况下，AT（2）受体似乎下调AT（1）受体介导的作用，导致细胞增殖减少，血清精氨酸加压素水平降低或血管收缩反应降低。此外，在神经元细胞系中，AT（2）受体发挥抗增殖作用并促进神经突生长，这种作用伴随着生长/分化相关基因表达模式的显著变化。
Angiotensin II (Ang II) has diverse physiological actions that lead, for instance, to increases in extracellular volume and peripheral vascular resistance and blood pressure, and it has also been implicated in the regulation of cell growth and differentiation. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors, designated AT, and AT(2). Most effects of Ang II are mediated by AT(1) receptors. Much less is known about the physiological role of AT(1) receptors. Recent evidence suggests involvement of AT(2) receptors in development, cell differentiation, apoptosis, and regeneration in various tissues. AT(1) and AT(2) receptors have been shown to exert counteracting effects on cellular growth and differentiation, vascular tone, and the release of arginine vasopressin. In each condition, the AT(2) receptor appears to down-modulate actions mediated by the AT(1) receptor, resulting in decreased cellular proliferation, decreased levels of serum arginine vasopressin levels, or decreased vasoconstrictor responses. In addition, in neuronal cell lines, the AT(2) receptor exerts antiproliferative actions and promotes neurite outgrowth, an effect accompanied by significant changes in the expression pattern of growth/differentiation-related genes.