Development of active fibroblast growth factor and its CNS action

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Both acidic and basic fibroblast growth factors(EGF) are elevated in the cerebrospinal fluid after food intake or glucose injection, that was detected both by a highly sensitive bioassay with Hydra and by a standard assay for growth factors, DNA synthesis-stimulating activity for BALB/c 3T3 cells (Hanai et al., 1987, 1989; Hanai 1989). The distribution of aFGF in the brain was dramatically changed with i.p. glucose injection, which was revealed by immunocytochemistry with anti-aFGF antibody. Application of the anti-aFGF antibody into the lateral hypothalamic area significantly increased the food intake first 3 h in rats. These results show that aFGF is one of the endogenous substances responsible for the regulation of food intake in the brain (Oomura et al., 1989). In in vivo experiments, FGF clearly suppressed the chemo-sensitive neuronal activities in the lateral hypothalamus of the conscious and reconscious rats. In order to see how FGF acts directly on the lateral hypothalamic neurons, the successive studies were made on the neurons acutely isolated from the lateral hypothalamus after the enzyme treatment. The electrical recordings were made in whole-cell mode by patch-clamp technique under the voltage-clamp condition. FGF had no effects on voltage-dependent ionic channels such as Na, K and Ca, and also on excitatory amino acids-gated channels. The GABA response shows run-down by decreasing intracellular ATP concentration. The intracellular ATP-sensitive GABA response was protected in 50% cells used in the presence of FGF. The electrical,and phartpacological properties of hypothalamic neurons, Purkinje cells, hippocampal CA1 neurons, amyglaloid neurons, and nucleus tractus solitarii neurons were also investigated (Akaike et al., 1989; Tokutomi et al., 1989; Shirasakiet al., 1990).