Development of receptor activation method for brain imaging with PET or SPECT

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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 … More 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