Elsevier

Brain Research

Volume 650, Issue 2, 11 July 1994, Pages 289-298
Brain Research

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

https://doi.org/10.1016/0006-8993(94)91794-9Get rights and content

Abstract

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 inreased theKd value of the D2 agonist [3H]N-propylnorapomorphine (NPA) binding sites by 42%. The CCKB antagonist PD134308 blocked this action. Kinetic analysis demostrated 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 theKH and theKL 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 theKH and theKL 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.

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