Cyclic AMP/protein kinase a signal attenuates Ca(2+)-induced fibroblast growth factor-1 synthesis in rat cortical neurons.
Fibroblast growth factor (FGF)-1 is increased in particular brain regions after birth, suggesting an involvement of some regulatory neuronal circuits. To address the neuronal activity responsible for FGF-1 synthesis, effects of various neurotransmitter receptor activation on cellular FGF-1 content were examined using cultured rat cortical neurons. Histamine, glutamate, carbachol, serotonin or gamma-aminobutyric acid (GABA) caused an increase of FGF-1 content. Because this effect was mimicked by (1) N-methyl-D-aspartate, a glutamatergic agonist; (2) Ca(2+) ionophore; (3) depolarization with high concentration of KCl, but was abolished in Ca(2+)-free medium, Ca(2+) influx was thought to trigger FGF-1 synthesis. Such Ca(2+)-mediated enhancement of FGF-1 synthesis, however, did not occur in the presence of norepinephrine (NE), but was restored by KT-5720, an inhibitor of protein kinase A (PKA), suggesting an interplay between Ca(2+)-activated and cAMP/PKA signals for neuronal FGF-1 synthesis. This mechanism was proved to function in vivo by stimulation of FGF-1 expression in neurons of the cerebral cortex after intracerebral administration of propranolol, an antagonist of adrenergic beta receptors. This demonstrates that FGF-1 synthesis is essentially upregulated by Ca(2+) influx through excitatory neuronal activities, but such an effect is abolished by neurotransmission that evokes cAMP/PKA signals. FGF-1 produced is thought to act on establishment and maintenance of particular neuronal circuits in the brain, which may be one of the ways neurotransmitters regulate brain function.
Kinukawa
Hideki
H
Laboratory of Molecular Biology, Gifu Pharmaceutical University Mitahora-higashi, Gifu, Japan.
Jikou
Takahiro
T
Nitta
Atsumi
A
Furukawa
Yoshiko
Y
Hashimoto
Manabu
M
Fukumitsu
Hidefumi
H
Nomoto
Hiroshi
H
Furukawa
Shoei
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005333:Fetus; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D016220:Fibroblast Growth Factor 1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium