The effects of cyclic AMP (cAMP)-related compounds on in vivo [3H]SCH 23390 binding to striatal dopamine D1 receptors were investigated using autoradiography in order to clarify the possible regulation of the cAMP-dependent mechanisms in the in vivo ligand-receptor bindings in the living brain. Intrastriatal infusion of the cAMP analogue, N6,2′-O-dibutyryl-cyclic AMP (db-cAMP; 5, 25 and 100 nmol/side) produced a dose-dependent increase of in vivo [3H]SCH 23390 binding in conscious rats. This increasing effect of [3H]SCH 23390 binding completely disappeared by 6 h after the infusion of db-cAMP. A similar increase of in vivo [3H]SCH 23390 binding to striatal D1 receptors was also observed by intrastriatal injection of 8-bromo-cyclic AMP (8Br-cAMP, 100 nmol/side). Pretreatment with Rp-cyclic AMP triethylamine (Rp-cAMPS, 100 nmol/side), an inhibitor of the cAMP-dependent protein kinase (PKA), completely blocked the increasing effect of [3H]SCH 23390 binding induced by db-cAMP. In contrast, in vitro [3H]SCH 23390 binding was not significantly altered by intrastriatal infusion of db-cAMP, which indicated that the maximum number of binding sites (Bmax) for D1 receptors was not changed. The kinetic analysis employed the graphical method indicated that a db-cAMP-induced increase of in vivo [3H]SCH 23390 binding was mainly due to an increase in the bimolecular association rate constant (kon). These results strongly indicate that the PKA-mediated phosphorylation may play a pivotal role in the regulating the in vivo [3H]SCH 23390 dopamine D1 receptor binding in intact rat brain.
- Dopamine D receptor
- In vivo [H]SCH 23390 receptor binding
- Protein kinase A
- Rat brain
ASJC Scopus subject areas