Document Detail

Evidence for nerve growth factor-potentiating activities of the nonpeptidic compound SR 57746A in PC12 cells.
MedLine Citation:
PMID:  7722483     Owner:  NLM     Status:  MEDLINE    
SR 57746A (1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride) exhibits neurotrophic activities in vivo and in vitro. We used the rat pheochromocytoma PC12 cell line to investigate in vitro cellular changes induced by SR 57746A. A significant increase in the percentage of cells bearing neurite-like processes was obtained in cells treated by SR 57746A and nerve growth factor (NGF) compared with NGF treatment alone. SR 57746A added alone, however, had no effect on morphogenesis or on survival of cells in serum-free medium. In contrast, SR 57746A induced a "priming" effect on PC12 cells for neurite outgrowth within 6 h of addition of the protein tyrosine kinase inhibitor genistein. An increase in alpha-actinin content resulted from treatment with SR 57746A. Expression of NGF-mediated acetylcholinesterase and choline acetyltransferase was enhanced within 5 days by SR 57746A. The molecule also induced rapid F-actin redistribution. Within 2 min of incubation, outgrowth of F-actin-containing filopodia was clearly visible at the cell periphery, as previously shown with NGF. It is interesting that this effect of SR 57746A could be mimicked by protein tyrosine kinase inhibitors and abolished by preincubation with sodium orthovanadate, a protein tyrosine phosphatase inhibitor.
A Pradines; M Magazin; P Schiltz; G Le Fur; D Caput; P Ferrara
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  64     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-05-23     Completed Date:  1995-05-23     Revised Date:  2005-07-21    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1954-64     Citation Subset:  IM    
Sanofi Recherche, Labège, France.
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MeSH Terms
Acetylcholinesterase / metabolism
Actinin / metabolism
Actins / analysis
Cell Differentiation / drug effects
Cell Survival / drug effects
Culture Media
Drug Synergism
Isoflavones / pharmacology
Naphthalenes / pharmacology*
Nerve Growth Factors / pharmacology*
Neurites / drug effects,  ultrastructure
PC12 Cells / metabolism,  ultrastructure*
Pyridines / pharmacology*
Serotonin Antagonists / pharmacology*
Signal Transduction / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Actins; 0/Culture Media; 0/Isoflavones; 0/Naphthalenes; 0/Nerve Growth Factors; 0/Pyridines; 0/Serotonin Antagonists; 11003-00-2/Actinin; 135354-02-8/xaliproden; 446-72-0/Genistein; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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