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

本文研究了磷酸二酯酶Ⅳ型选择性抑制剂咯利普兰对小鼠脑内多巴胺D_1和多巴胺D_2受体结合的影响。咯利普兰可剂量依赖性地降低小鼠纹状体多巴胺D_1和多巴胺D_2受体结合率。对^3 H-SCH 23390结合的动力学分析表明，咯利普兰降低了^3H-23390结合的输入速率常数（k_3=Kon/Bmax）。在体饱和实验中，给予咯利普兰后小鼠D_1受体的Bmax无明显变化。通过用咯利普兰预处理，还观察到毒蕈碱乙酰胆碱受体的体内结合显著减少。由于咯利普兰增加了脑内cAMP含量，这些结果表明cAMP在完整脑内受体结合中起重要作用。Db-cAMP可显著增加^3 H-SCH 23390 B，并呈剂量依赖性 ...更多信息 在大鼠纹状体中的iding。用蛋白激酶A（PKA）抑制剂Rp-cAMPs预处理后，这种结合几乎完全被抑制，表明cAMP/PKA系统在多巴胺D_1受体结合中起重要作用。注射db-cAMP后，多巴胺D_1受体与^~ 3 H-NMSP和^~ 3 H-NMPB的结合也增加，提示cAMP/PKA系统在多巴胺D_1受体结合中起重要作用。微量注射db-cAMP后，大鼠脑内^3 H-NMSP和^3 H-NMPB的结合也明显增加，提示可能是由于蛋白质磷酸化引起的脑内微环境的整体改变。结果表明，cAMP/PKA系统在完整脑组织中参与了配体-受体相互作用和底物-酶反应等分子间相互作用过程。少

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