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Dopamine D1 receptors are involved in the modulation of D2 receptors induced by cholecystokinin receptor subtypes in rat neostriatal membranes

Li, X.M.; Hedlund, P.B.; Agnati, L.F.; Fuxe, K.

Brain Research 650(2): 289-298

1994


ISSN/ISBN: 0006-8993
PMID: 7953694
DOI: 10.1016/0006-8993(94)91794-9
Accession: 008499489

The action of cholecystokinin octapeptide (CCK-8) on rat neostriatal dopamine (DA) D-2 receptors was evaluated in membrane binding experiments. 0.1 nM of CCK-8 increased the K-d value of the D-2 agonist (3H)N-propylnorapomorphine (NPA) binding sites by 42%. The CCK-B 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 K-H and the K-L values of DA for the D-2 antagonist (3H)raclopride binding sites by 56% and 50%, respectively. Both the CCK-A antagonist L364718 and the CCK-B antagonist PD134308 blocked this effect. The D, antagonist SCH23390 counteracted the CCK-8 induced decrease in the K-H and the K-L values of DA, and allowed 1 nM of CCK-8 to produce a significant increase in the IC-50 value of NPA for the (3H)raclopride binding sites. These results indicate that CCK-8 can reduce the affinity of the neostriatal D, agonist binding sites, but increase the affinity of D-2 receptors for DA. D-1 receptors may exert a switching role in the modulation of the neostriatal D-2 receptors by the CCK receptors.

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