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Evidence for Nerve Growth Factor‐Potentiating Activities of the Nonpeptidic Compound SR 57746A in PC12 Cells
Author(s) -
Pradines Anne,
Magazin Marilyn,
Schiltz Pascal,
Le Fur Gérard,
Caput Daniel,
Ferrara Pascual
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64051954.x
Subject(s) - nerve growth factor , neurite , neurotrophin , filopodia , microbiology and biotechnology , sodium orthovanadate , tyrosine kinase , chemistry , basic fibroblast growth factor , endocrinology , biology , protein tyrosine phosphatase , medicine , in vitro , growth factor , kinase , biochemistry , signal transduction , actin , receptor
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 α‐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.