receptor blockers did not affect fibroblast growth factor (FGF) induction of c -fos 
mRNA and only partially blocked K + , TPA, zinc, and VIP induction of c -fos 
mRNA. 
However, the most novel aspect of this study was the observation that 
pretreatment of cultured cortical neurons with noncompetitive (MK801) and 
competitive (CPP and APH) NMDA antagonists completely blocked the 
induction of FLI by all agents tested. Treatment of cultured cortical neurons 
with NMDA antagonists alone had no effect on c -fos mRNA or FLI. In addition, 
treatment of cultures with NMDA antagonists had no effect on total protein 
synthesis as measured by 3 H leucine into trichloroacetic acid-precipitated 
proteins. Since the polyclonal antibody used in this study detects both Fos 
protein and two lower molecular weight Fos-related antigens (Aronin et al. 1990, 
1991), the data demonstrate that the NMDA antagonists prevent induction of 
Fos protein and Fos-related antigens. 
DISCUSSION 
Glutamate induces c-fos mRNA and Fos protein in a small subpopulation (8 to 
10 percent) of cultured cortical neurons. This induction appears to occur via the 
NMDA receptor since both competitive and noncompetitive NMDA receptor 
blockers prevent glutamate induction of c-fos mRNA and Fos protein. Similar 
results have been observed in cultured cerebellar granule cell neurons (Szekely 
etal. 1989). 
The data also show that K + , TPA, bFGF, zinc, VIP, and db-cAMP induce c-fos 
mRNA and Fos protein in a similar small subpopulation (8 to 10 percent) of 
cultured cortical neurons. Moreover, although NMDA receptor blockers prevent 
c-fos mRNA induction by glutamate and db-cAMP, other agents like K + , TPA, 
bFGF, zinc, and VIP all induce c-fos mRNA in the presence of NMDA receptor 
blockers. These observations prove that induction of c-fos mRNA via these 
signaling pathways is not linked to release of glutamate and/or activation of 
the NMDA receptor. The data also show that several agents (including NGF, 
PDGF, EGF, NPY, somatostatin, NMDA antagonists, and carbachol) do not 
induce the c-fos gene in cultured cortical neurons. 
The unexpected finding of this study was that NMDA receptor blockers do 
prevent the induction of FLI by all agents tested, including K + , TPA, bFGF, 
zinc, VIP, and db-cAMP as well as glutamate. The authors believe that the 
results are not artifactual since (1) the agents did induce c-fos mRNA; (2) 
three chemically different NMDA antagonists blocked induction of Fos protein, 
but not c-fos mRNA; (3) total protein synthesis was not affected by the NMDA 
antagonists; and (4) graded doses of NMDA antagonists produced graded 
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