Cyclic AMP/protein kinase a signal attenuates Ca2+-induced fibroblast growth factor-1 synthesis in rat cortical neurons

• Published in: Journal of neuroscience research 2004-08, Vol.77 (4), p.487-497
• Main Authors: Kinukawa, Hideki, Jikou, Takahiro, Nitta, Atsumi, Furukawa, Yoshiko, Hashimoto, Manabu, Fukumitsu, Hidefumi, Nomoto, Hiroshi, Furukawa, Shoei
• Format: Article
• Language: English
• Subjects: Ca2; cyclic AMP; fibroblast growth factor-1 (FGF-1); neurotransmitter; neurotrophic factor; protein kinase; synthesis
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20164

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 γ‐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) Ca2+ ionophore; (3) depolarization with high concentration of KCl, but was abolished in Ca2+‐free medium, Ca2+ influx was thought to trigger FGF‐1 synthesis. Such Ca2+‐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 Ca2+‐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 β receptors. This demonstrates that FGF‐1 synthesis is essentially upregulated by Ca2+ 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. © 2004 Wiley‐Liss, Inc.