Angiotensin II induction of neurite outgrowth by AT2 receptors in NG108-15 cells. Effect counteracted by the AT1 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 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.
Laflamme
L
L
Service of Endocrinology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, J1H 5N4 Quebec, Canada.
Gasparo
M
M
Gallo
J M
JM
Payet
M D
MD
Gallo-Payet
N
N
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D008858:Microscopy, Phase-Contrast; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014404:Tubulin; D016875:tau Proteins; D000804:Angiotensin II