| Co-Investigator(Kenkyū-buntansha) |
OOMURA Yutaka Research Inst. for omental Medicine, Dept of Central Nervous functic Control Sys, 和漢薬研究所, 客員教授 (30019517)
SASAKI Kazuo Yoyama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (60042826)
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| Research Abstract |
Fibroblast Growth Factor (FGF) was identified by its ability to promote the growth of fibroblast. The presence of significant amount of GFG found in the brain where no cell-proliferation occurs, suggests the physiological significance of FGF in the brain. Recently a line of evidences suggest that FGF may be a neural substance involved in learning and memory as well as a neurotrophic factor which is important for survival of neural cells. Thus FGF is a good candidate for the drug to prevent or treat the losing ability of learning and memory along with aging. however FGF has a potential risk of cancers because of its role in cell proliferation. Thus it is important to develop modified FGF which is selectively effective in the brain and lacking the mitogenic activity. As a first step to develop such a modefied FGF, we have investigated which region of FGF is essential for the activity in the brain using protein engineering techniques. The effects of acidic fibroblast growth factor (aFGF), basic FGF(bFGF), and related peptide modified from aFGF, on food and intake were investigated. Infusion of aFGF and bFGF into the third cerebral venticle significantly suppressed food intake. The potency of aFGF was 1.5 that of bFGF in food intake inhibition. Infusion of a carboxyl-terminal fragment of aFGF, aFGF-(114-140), did knot affect food intake, whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly inhibitory. Other amino-terminal fragments, aFGF-(1-20) and aFGF-(1-29), did knot affect food intake. However, [Ala16]aFGF-(1-29) in which the cysteine residue at position 16 was replaced with alanine significantly suppressed food intake. The results suggest that aFGF, bFGF and some amino-terminal peptide of aFGF participate in the central regulation of food intake.
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