Activation of the AT(2) receptor of angiotensin II induces neurite outgrowth and cell migration in microexplant cultures of the cerebellum

Microexplant cultures from three-day-old rats were used to investigate whet her angiotensin II (Ang II), through its AT(1) and AT(2) receptors, could b e involved in the morphological differentiation of cerebellar cells. Specif ic activation of the AT(2) receptor during 4-day treatment induced two majo r morphological changes. The first was characterized by increased elongatio n of neurites. The second change was cell migration from the edge of the mi croexplant toward the periphery. Western blot analyses and indirect immuno fluorescence studies revealed an increase in the expression of neuron-speci fic beta III-tubulin, as well as an increase in expression of the microtubu le-associated proteins tau and MAP2. These effects were demonstrated by co- incubation of Ang II with 1 mu M DUP 753 (AT(1) receptor antagonist) or wit h 10 nM CGP 42112 (AT(2) receptor agonist) but abolished when Ang II was co -incubated with 1 mu M PD 123319 (AT(2) receptor antagonist), indicating th at differentiation occurs through AT(2) receptor activation and that the AT (1) receptor inhibits the AT(2) effect. Taken together, these results demon strate that Ang II is involved in cerebellum development for both neurite o utgrowth and cell migration, two important processes in the organization of the various layers of the cerebellum.