Regulation of dopamine D₂ receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCK_B and D2L receptor cDNAs

Alteration in dopamine (DA) and/or cholecystokinin (CCK) transmission in the CNS may be of relevance for schizophrenia. Previous findings in striatal membranes give indications of a modulation of DA D₂ receptor affinity by CCK_B receptor activation. In the present study receptor binding studies were performed in a mouse fibroblast cell line (L-hD21/CCK), expressing both human D₂ receptors (long form, D₂L) and human CCK_B receptors, and binding sites for [³H]CCK-SS (sulfated CCK octapeptide), the D₂ agonist [³H]NPA and the D₂ antagonist [³H]raclopride were found and characterized in saturation and competition experiments. 1 nM of CCK-8 caused a significant 38% increase in the K_D value of the D₂ agonist [³H]NPA binding sites in the L-hD21/CCK cell membranes. This change was blocked by the CCK_B receptor antagonist PD 134308 (50 nM). Furthermore, 1 nM of CCK-8 increased the K_D value of the D₂ antagonist [³H]raclopride binding sites by 34% (P < 0.05) in the L-hD21/CCK cell membranes. Control cells (L-hD21 cells) expressing D₂L receptors showed no specific [³H]CCK-SS binding sites and no modulation by CCK-8 of the D₂L receptors. These findings indicate a modulation of the D₂L receptor affinity by activation of the CCK_B receptor also when they are coexpressed in a fibroblast cell line. One possible explanation of these data may include a receptor-receptor interaction between the CCK_B and D₂L receptors.