Angiotensin II induction of neurite outgrowth by AT(2) receptors in NG108-15, cells - Effect counteracted by the AT(1) receptors

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 mor 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 AT(2) receptor may be inferred since: (a) these cells contain only AT(2) receptors; (b) the effects are mimicked by CGP 42112 (an AT(2) receptor agonist); (c) they are not suppressed by the addition of DUP 753 (an AT(1) receptor antagonist); and (d) are abolished by co-incubation with PD 123319 (an AT(2) 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 AT(1) receptor. These results indicate that the AT(2) 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 AT(1) receptor inhibit the process of differentiation induced by dibutyryl cAMP, whereas the AT(2) receptors potentiate this effect, illustrating negative cross-talk interaction between the two types of Ang II receptors.