REGULATION OF DOPAMINE D-2 RECEPTOR AFFINITY BY CHOLECYSTOKININ-OCTAPEPTIDE IN FIBROBLAST CELLS COTRANSFECTED WITH HUMAN CCKB AND D(2)L 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 D-2 recepto r affinity by CCKB receptor activation. In the present study receptor binding studies were performed in a mouse fibroblast cell line (L-hD21 /CCK), expressing both human D-2 receptors (long form, D(2)L) and huma n CCKB receptors, and binding sites for [H-3]CCK-8S (sulfated CCK octa peptide), the D-2 agonist [H-3]NPA and the D-2 antagonist [H-3]raclopr ide were found and characterized in saturation and competition experim ents. 1 nM off CCK-8 caused a significant 38% increase in the K-D valu e of the D-2 agonist [H-3]NPA binding sites in the L-hD21/CCK cell mem branes. This change was blocked by the CCKB receptor antagonist PD 134 308 (50 nM). Furthermore, 1 nM of CCK-8 increased the K-D value of the D-2 antagonist [H-3]raclopride binding sites by 34% (P < 0.05) in the L-hD21/CCK cell membranes. Control cells (L-hD21 cells) expressing D( 2)L receptors showed no specific [H-3]CCK-8S binding sites and no modu lation by CCK-8 of the D(2)L receptors. These findings indicate a modu lation of the D(2)L receptor affinity by activation of the CCKB recept or also when they are coexpressed in a fibroblast cell line. One possi ble explanation of these data may include a receptor-receptor interact ion between the CCKB and D(2)L receptors.