title: Regulation of dopamine D2 receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCKB and D2L receptor cDNAs.
abstract: 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 CCKB receptor activation. In the present study receptor binding studies were performed in a mouse fibroblast cell line (L-hD2l/CCK), expressing both human D2 receptors (long form, D2L) and human CCKB receptors, and binding sites for [3H]CCK-8S (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 KD value of the D2 agonist [3H]NPA binding sites in the L-hD2l/CCK cell membranes. This change was blocked by the CCKB receptor antagonist PD 134308 (50 nM). Furthermore, 1 nM of CCK-8 increased the KD value of the D2 antagonist [3H]raclopride binding sites by 34% (P < 0.05) in the L-hD2l/CCK cell membranes. Control cells (L-hD2l cells) expressing D2L receptors showed no specific [3H]CCK-8S 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 CCKB 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 CCKB and D2L receptors.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Dasgupta
authors.forename: X M
authors.initials: XM
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Jansson
authors.forename: U B
authors.initials: UB
authors.lastname: Finnman
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: A
authors.initials: A
authors.lastname: Rinken
authors.forename: E
authors.initials: E
authors.lastname: Arenas
authors.forename: L F
authors.initials: LF
authors.lastname: Agnati
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D012844:Sincalide