Document Detail

Contribution of bradykinin and nitric oxide to AT2 receptor-mediated differentiation in PC12 W cells.
MedLine Citation:
PMID:  12694402     Owner:  NLM     Status:  MEDLINE    
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 (10-7 m) increased the outgrowth of medium and large neurites by mean +/- SEM 20.2 +/- 2.3 and 6.6 +/- 1.4 compared with 1.66 +/- 0.5 and 0.1 +/- 0.06 neurites per 100 cells in control. Cellular cyclic GMP content increased by 50-250% with angiotensin II at concentrations of 10-6-10-4 m. Both blockade of AT2 receptors and of nitric oxide synthase markedly reduced angiotensin II-induced neurite outgrowth and cyclic GMP production. In contrast, B2 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 AT2 receptor and further enhanced by bradykinin B2 receptor blockade.
Yi Zhao; Torsten Biermann; Claudia Luther; Thomas Unger; Juraj Culman; Peter Gohlke
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  85     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-15     Completed Date:  2003-06-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  759-67     Citation Subset:  IM    
Institute of Pharmacology, Christian-Albrechts University of Kiel, Kiel, Germany.
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MeSH Terms
Alkaloids / pharmacology
Angiotensin II / pharmacology
Bradykinin / metabolism*,  pharmacology
Cell Count
Cell Differentiation / drug effects,  physiology*
Cyclic GMP / analogs & derivatives*,  metabolism,  pharmacology
Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Neurites / classification,  drug effects,  physiology
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Nitroprusside / pharmacology
PC12 Cells
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin / agonists,  antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Alkaloids; 0/Carbazoles; 0/Enzyme Inhibitors; 0/Indoles; 0/Nitric Oxide Donors; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 10102-43-9/Nitric Oxide; 11128-99-7/Angiotensin II; 126643-37-6/KT 5823; 15078-28-1/Nitroprusside; 31356-94-2/8-bromocyclic GMP; 58-82-2/Bradykinin; 7665-99-8/Cyclic GMP; EC GMP-Dependent Protein Kinases

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