Increment of in vivo binding of [3H]SCH 23390, a dopamine D1 receptor ligand, induced by cyclic AMP-dependent protein kinase in rat brain.
The effects of cyclic AMP (cAMP)-related compounds on in vivo [(3)H]SCH 23390 binding to striatal dopamine D(1) 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 [(3)H]SCH 23390 binding in conscious rats. This increasing effect of [(3)H]SCH 23390 binding completely disappeared by 6 h after the infusion of db-cAMP. A similar increase of in vivo [(3)H]SCH 23390 binding to striatal D(1) 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 [(3)H]SCH 23390 binding induced by db-cAMP. In contrast, in vitro [(3)H]SCH 23390 binding was not significantly altered by intrastriatal infusion of db-cAMP, which indicated that the maximum number of binding sites (B(max)) for D(1) receptors was not changed. The kinetic analysis employed the graphical method indicated that a db-cAMP-induced increase of in vivo [(3)H]SCH 23390 binding was mainly due to an increase in the bimolecular association rate constant (k(on)). These results strongly indicate that the PKA-mediated phosphorylation may play a pivotal role in the regulating the in vivo [(3)H]SCH 23390 dopamine D(1) receptor binding in intact rat brain.
Abe
Kohji
K
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. kohji.abe@shionogi.co.jp
Hosoi
Rie
R
Momosaki
Sotaro
S
Kobayashi
Kaoru
K
Ibii
Nobuhiro
N
Inoue
Osamu
O
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
D001552:Benzazepines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases