YAMAMOTO Hideyuki Kumamoto University School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
FUKUNAGA Kohji Kumamoto University School of Medicine, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)
|Budget Amount *help
¥8,200,000 (Direct Cost : ¥8,200,000)
Fiscal Year 1996 : ¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1995 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Neurons and related cells in the brain receive diverse stimuli for receptors in the plasma membranes, which include nerve impulses, neurotransmitters, neuropeptides, autacoids, hormones, cytokines, and growth factors. Responses of the cells include various types such as the production of second messengers and activation of tyrosine kinases. The intracellular calcium ion (Ca^<2+>) is established to be one of second messengers and its concentration in the cells is strictly regulated. The purposes of the present study are to elucidate the intracellular responses elicited by the increase in Ca^<2+> on the basis of stimulation of receptors in the plasma membranes. We used primarily cultured neurons of the hippocampus, astrocytes from cerebrum and cultured granule cells from cerebellum, established cell lines such as PC12 cells. NG108-15 cells, C6 glioma cells, fibroblast 3Yl cells and brain slices. In an attempt to elucidate the functions of the central nervous system through Ca^<2+> signaling pathways, we examined the dynamic state of activation of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) in the cell systems. We found that CaM kinase II is activated through elevation of intracellular Ca^<2+> in response to the extracellular stimuli and is involved in the cellular functions of the central nervous system, such as neuronal differentiation of PC12 cells, gene expression in astrocytes and long-term potentiation in the CAl area of the hippocampus. Ca^<2+> is also involved in the activation of mitogenactivated protein kinase in neurons and astrocytes. Furthermore, with concomitant activation of the enzyme, phosphorylation of endogenous substrates was studied.