Dopamine D1 receptors are involved in the modulation of D2 receptors induced by cholecystokinin receptor subtypes in rat neostriatal membranes.
The action of cholecystokinin octapeptide (CCK-8) on rat neostriatal dopamine (DA) D2 receptors was evaluated in membrane binding experiments. 0.1 nM of CCK-8 increased the Kd value of the D2 agonist [3H]N-propylnorapomorphine (NPA) binding sites by 42%. The CCKB antagonist PD134308 blocked this action. Kinetic analysis demonstrated that this effect of CCK-8 was related to a reduction by 45% of the association rate constant of [3H]NPA. In contrast, 1 nM of CCK-8 decreased the KH and the KL values of DA for the D2 antagonist [3H]raclopride binding sites by 56% and 50%, respectively. Both the CCKA antagonist L364718 and the CCKB antagonist PD134308 blocked this effect. The D1 antagonist SCH23390 counteracted the CCK-8 induced decrease in the KH and the KL values of DA, and allowed 1 nM of CCK-8 to produce a significant increase in the IC50 value of NPA for the [3H]raclopride binding sites. These results indicate that CCK-8 can reduce the affinity of the neostriatal D2 agonist binding sites, but increase the affinity of D2 receptors for DA. D1 receptors may exert a switching role in the modulation of the neostriatal D2 receptors by the CCK receptors.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
X M
XM
Li
P B
PB
Hedlund
L F
LF
Agnati
K
K
Fuxe
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D011949:Receptors, Cholecystokinin; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; C009074:N-n-propylnorapomorphine; D012844:Sincalide; D001058:Apomorphine; D004298:Dopamine