Details

Autor(en) / Beteiligte

• Zhao, Y
• Biermann, T
• Luther, C
• Unger, T
• Culman, J
• Gohlke, P

Titel

Contribution of bradykinin and nitric oxide to AT sub(2) receptor-mediated differentiation in PC12 W cells

Ist Teil von

• Journal of neurochemistry, 2003-05, Vol.85 (3), p.759-767

Erscheinungsjahr

2003

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• We investigated the effect of angiotensin II on intracellular cyclic GMP content and neurite outgrowth as an indicator of cell differentiation in PC12 W cells. Neurite outgrowth was examined by phase-contrast microscopy. Outgrown neurites were classified as small, medium and large, and were expressed as neurites per 100 cells. Angiotensin II (10 super(-7) m) increased the outgrowth of medium and large neurites by mean plus or minus SEM 20.2 plus or minus 2.3 and 6.6 plus or minus 1.4 compared with 1.66 plus or minus 0.5 and 0.1 plus or minus 0.06 neurites per 100 cells in control. Cellular cyclic GMP content increased by 50-250% with angiotensin II at concentrations of 10 super(-6)-10 super(4) m. Both blockade of AT sub(2) receptors and of nitric oxide synthase markedly reduced angiotensin II-induced neurite outgrowth and cyclic GMP production. In contrast, B sub(2) receptor blockade had no effect or even increased these angiotensin II effects. Sodium nitroprusside and 8-bromo-cyclic GMP both mimicked the effects of angiotensin II on cell differentiation. The protein kinase G inhibitor KT-5823 inhibited the neurite outgrowth induced by both angiotensin II and 8-bromo-cyclic GMP. Our results demonstrate that angiotensin II can stimulate cell differentiation in PC12 W cells by nitric oxide-related and cyclic GMP-dependent mechanisms. The effects of angiotensin II on cell differentiation and cyclic GMP production were mediated via the AT sub(2) receptor and further enhanced by bradykinin B sub(2) receptor blockade.