| Project/Area Number |
13670935
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Osaka University |
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Principal Investigator |
INOUE Osamu Faculty of Medicine, Professor, 医学部, 教授 (50159969)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Kazutoshi National Institute of radiological Sciences Head, Radiopharmaceutical Chemistry Section, ユニット長(研究職) (90162932)
HOSOI Rio Faculty of Medicine, Staff, 医学部, 教務職員 (30291446)
KOBAYASHI Kaoru Faculty of Medicine, Associate Professor, 医学部, 助教授 (90256933)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | cAMP / NO / receptor binding / in vivo / in vitro / インビドロ |
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| Research Abstract |
Effects of rolipram, a selective phosphodiesterase type IV inhibitor, upon dopamine D_1 and dopamine D_2 receptor biding in mouse brain were investigated. Rolipram significantly and dose-dependently decreased both dopamine D_1 and dopamine D_2 receptor binding in mouse striatum. The kinetic analysis of ^3H-SCH23390 binding revealed that rolipram decreased the input rate constant (k_3=Kon/Bmax) of ^3H-23390 binding. In vivo saturation experiment on ^3H-SGH23390 binding showed no significant change in Bmax of D_1 receptor in rolipram-treared mice. A significant reduction in in vivo binding of muscarinic acetyloholine receptor was also observed by pretreated with rolipram. As rolipram increased cAMP content in the brain, these results indicated an important role of cAMP upon receptor biding in intact brain.
Effects of microinjection of db-cAMP into rat striatum on ^3H-SGH23390 binding were also examined by autoradiography. Db-cAMP significantly and dose-dependently increased ^3H-SCH23390 b
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iding in rat striatum. This increase in binding was almost completely inhibited by pretreated with Rp-cAMPs, a protein kinase A(PKA) inhibitor, which indicated an important role of cAMP/PKA system on dopamine D_1 receptor biding. ^3H-NMSP biding as well as ^3H-NMPB binding was also increased by microinjection of db-cAMP, which indicated an important role of cAMP/PKA system on dopamine D_1 receptor biding. ^3H-NMSP biding as well as ^3H-NMPB biding was also increased by microinjection of db-cAMP, which indicated global changes in microenvironment induced by phospholylation of protein might be occurred.
Another important finding is that Rp-cAMPs significantly increased glucose metabolism in rat brain although the regional blood flow was decreased. The increase in glucose metabolism was found to be due to increase in phospholylation process of glucose by hexokinase.
In conclusion, cAMP/PKA system has important role on molecule interaction process including ligand-resepter interaction and substrate-enzyme reaction in intact brain. Less
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