ANGIOTENSIN-II AND NGF DIFFERENTIALLY INFLUENCE MICROTUBULE PROTEINS IN PC12W CELLS - ROLE OF THE AT(2) RECEPTOR

Angiotensin AT(2) receptors have been shown to play a role in cell dif ferentiation characterized by neurite outgrowth in neuronal cells of d ifferent origin. To further investigate AT(2) receptor-mediated events leading to neurite formation, we examined the effect of AT(2) recepto r stimulation on the microtubule components, beta-tubulin, MAP1B and M AP2, by Western blot analysis and immunofluorescence in quiescent and nerve growth factor (NGF)-differentiated PC12W cells. These proteins a re involved in neurite extension and neuronal maturation. Whereas NGF (0.5, 10, and 50 ng/ml) up-regulated these proteins after 3 days of st imulation, angiotensin II (ANG II; 10(-7) M) induced a different patte rn. In quiescent PC12W cells, AT(2) receptor stimulation up-regulated polymerized beta-tubulin and MAP2 but downregulated MAP1B protein leve ls. In PC12W cells, differentiated by NGF (0.5 ng/ml), ANG II: elevate d polymerized beta-tubulin and reduced MAP1B. All ANG II effects were abolished by the AT(2) receptor antagonist PD123177 (10(-5) M) but not affected by the AT(1) receptor antagonist losartan (10(-5) M). These results implicate a specific role of AT(2) receptors in cell different iation and nerve regeneration via regulation of the cytoskeleton. (C) 1998 Elsevier Science B.V.