Laflamme L, Gasparo M, Gallo J M, Payet M D, Gallo-Payet N
Service of Endocrinology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, J1H 5N4 Quebec, Canada.
J Biol Chem. 1996 Sep 13;271(37):22729-35. doi: 10.1074/jbc.271.37.22729.
In the present study, 3-day treatment of nondifferentiated NG108-15 cells with 100 nM angiotensin II (Ang II) induces morphological differentiation of neuronal cells characterized by the outgrowth of neurites. These morphological changes are correlated with an increase in the level of polymerized tubulin and in the level of the microtubule-associated protein, MAP2c. Mediation by the AT2 receptor may be inferred since: (a) these cells contain only AT2 receptors; (b) the effects are mimicked by CGP 42112 (an AT2 receptor agonist); (c) they are not suppressed by the addition of DUP 753 (an AT1 receptor antagonist); and (d) are abolished by co-incubation with PD 123319 (an AT2 receptor antagonist). Application of Ang II in dibutyryl cAMP-differentiated cells (which contain both types of receptors) induces neurite retraction, an effect mediated by the AT1 receptor. These results indicate that the AT2 receptor of Ang II induces neuronal differentiation, which is initiated through an increase in the levels of MAP2c associated with tubulin. Moreover, our results demonstrate that the AT1 receptor inhibit the process of differentiation induced by dibutyryl cAMP, whereas the AT2 receptors potentiate this effect, illustrating negative cross-talk interaction between the two types of Ang II receptors.
在本研究中，用100 nM血管紧张素II（Ang II）对未分化的NG108 - 15细胞进行3天处理可诱导神经元细胞发生形态分化，其特征为神经突生长。这些形态变化与聚合微管蛋白水平及微管相关蛋白MAP2c水平的升高相关。可推断AT2受体起介导作用，原因如下：（a）这些细胞仅含有AT2受体；（b）CGP 42112（一种AT2受体激动剂）可模拟这些效应；（c）添加DUP 753（一种AT1受体拮抗剂）不会抑制这些效应；（d）与PD 123319（一种AT2受体拮抗剂）共同孵育可消除这些效应。在二丁酰环磷腺苷分化的细胞（含有两种类型的受体）中应用Ang II会诱导神经突回缩，这是由AT1受体介导的效应。这些结果表明，Ang II的AT2受体可诱导神经元分化，这是通过与微管蛋白相关的MAP2c水平升高而启动的。此外，我们的结果表明，AT1受体抑制二丁酰环磷腺苷诱导的分化过程，而AT2受体增强这种效应，这说明了两种类型的Ang II受体之间存在负性串扰相互作用。
