Basic fibroblast growth factor selectively amplifies the functional state of neurons producing neuropeptide Y but not somatostatin in cultures of fetal brain cells: evidence for a cooperative interaction with insulin-like growth factor-I.
The role of basic fibroblast growth factor (bFGF) in regulating the functional state of neuropeptide Y (NPY) neurons in the brain was investigated, using aggregate cultures, derived from 17-day-old fetal rat cortex maintained for 16 days in serum-free medium, as a model. The criterion for the functional state was NPY production in response to a 24-h exposure to forskolin + phorbol 12-myristate 13-acetate (For + PMA). bFGF (0.1 nM) induced a approximately 2-fold increase in NPY production under basal conditions as well as after For + PMA (p < 0.001 vs control). To address the possibility that bFGF may interact with other growth factors, we assessed the effect of bFGF in the presence of long R3-insulin-like growth factor-I (l-IGF-I; 1 nM) and found that NPY production in response to For + PMA was even greater than with bFGF alone (2-fold; p < 0.001); even though l-IGF-I by itself was ineffective; suggesting that bFGF is the driving force of this amplification. To assess the selectivity of this process, we evaluated SRIF production in response to For + PMA and found that it was not amplified by bFGF, l-IGF-I, or bFGF + l-IGF-I. These results are consistent with bFGF selectively amplifying the functional state of the cAMP and protein kinase C (PKC) pathways leading to increased NPY-production, with cooperative interaction(s) between bFGF and IGF-I, and with a role for bFGF and IGF-I in the developmental expression/survival of the NPY neurons.
Barnea
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Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas 75235.
Cho
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D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009478:Neuropeptide Y / Q000096:biosynthesis*; D013004:Somatostatin / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009478:Neuropeptide Y; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013755:Tetradecanoylphorbol Acetate