OHTA Mitsuhiro Utano National Hospital, Investigator, 臨床研究部, 研究員
FUJIMOTO Masafumi Sionogi Pharmaceutical, Chief Investigato, 創薬第二研究所, 主席研究員
OZAKI Kei-ichi Kyoto Univ.Grad.Sch.of Pharm.Sci., Assit.Professor, 薬学研究科, 助手 (50252466)
|Budget Amount *help
¥16,400,000 (Direct Cost: ¥16,400,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
Insulin receptor-related receptor (IRR) is a member of the insulin receptor family. However, its endogenous ligand and physiological roles are unknown. To elucidate the physiological roles of IRR, an orphan receptor, in the brain, we examined its expression at mRNA and protein levels in the brain by in situ hybridization and immunohistochemistry, respectively. The expression of IRR mRNA in the brain was highly restricted to the forebrain including the nucleus of the diagonal band, medial septal nucleus, ventral pallidum, accumbens nucleus and caudate putamen, and the brainstem including the prepositus hypoglossal nucleus, medial vestibular nucleus, gigantocell reticular nucleus, paragigantocellular nucleus and ventral cochlear nucleus. Most IRR mRNA-positive cells in the forebrain but not in the brainstem were cholinergic neurons. However, most LRR mRNA in the forebrain and brainstem was coexpressed with that of trkA, a high affinity receptor for nerve growth factor. IRR-immunoreactive cell bodies were also detected in the forebrain and brainstem. The pattern of IRR immunoreactivity was similar to that of IRR mRNA.Its restricted pattern indicates that IRR plays unique roles in the brain, in contrast to insulin and insulin-like growth factor-I receptors, other members of the insulin receptor family, which are widely expressed in the brain.
We isolated the cDNA encoding members, FGF-7, FGF-18 and FHF-4 of the fibroblast growth factor (FGF) family from rat embryos. FGF-17 and FGF-18 are most similar to FGF-8. In contrast, FHF-4 is a member of the FHF subfamily. These FGFs have typical signal sequences at their amino-termini., and were expressed in developing and/or adult brain. The FGFs Recombinant FGFs, which were efficiently secreted by High Five insect cells infected with recombinant baculovirus containing the cDNA, induced neurite outgrowth in PC12 cells. These results indicate that FGF-l 7, FGF-18 and FHF-4 are expected to be potential neurotrophic factors.