| Project/Area Number |
05807173
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Meikai University |
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Principal Investigator |
NAKANISHI Nobuo (1994) Meikai Univ., Biochem., Assistant Prof., 歯学部, 講師 (20118574)
山田 正三 (1993) 明海大学, 歯学部, 教授 (30049358)
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| Co-Investigator(Kenkyū-buntansha) |
中西 信夫 明海大学, 歯学部, 講師 (20118574)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Cyclic AMP / Protein phosphorylation / Catecholamine uptake / Vesicular amine transport / Neurotransmitter / Extracellular amine / Pheochromocytoma PC12 / Dopaminergic neuron / protein kinase A / pheochromcytoma PC12 / dopaminergis neuron |
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| Research Abstract |
We had found that cyclic AMP (cAMP) inhibited catecholamine transport and increased the extracellular dopamine level in pheochromocytoma PC12 cell culture, a model for monoaminergic neurons. An aim of the present study is to clarify whether cAMP regulates the monoamine transport and extracellular monoamine neurotransmitter in the CNS and PNS.With using a brain microdialysis technique, we examined cAMP effect on extracellular dopamine level in striatum regions of freely moving rat. Mechanisms of this cAMP action on the monoamine transport was also examined with PC12 cells in culture.
Dialytic infusion of dibutyryl cAMP (dBcAMP) into rat striatum resulted in an increase in extracellular dopamine level and this dBcAMP effect was detectable under the low Ca^<2+> concentration in the extracellular fluid where the dopamine increase was not observed by the infusion of striatum with high K^+ (50mM). Comparison of the dBcAMP effect on extracellular dopamine with monoamine transport inhibiors, nomifensine and reserpine, also supported the idea that cAMP increases extracellular dopamine by inhibiting the amine transport in dopaminergic neurons in the striatum. Effect of dBcAMP on a level of dihydroxyphenylacetic acid (DOPAC), a dopamine-derived metabolite, was also examined and was compared with those of the monoamine transport inhibitors. dBcAMP showed an effect similar to that of reserpine, suggesting the inhibition of monoamine transport through secretory vesicular membrane by dBcAMP.With PC12 cells, we confirmed that cAMP inhibited catecholamine reuptake and increased extracellular dopamine by down-regulating the vesicular monoamine transport.
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