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

Sarmila Dasgupta, Xi Ming Li, Anders Jansson, Ulla Britt Finnman, Toshimitsu Matsui, Ago Rinken, Ernest Arenas, Luigi F. Agnati, Kjell Fuxe

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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-hD21/CCK), expressing both human D2 receptors (long form, D2L) and human CCKB 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 KD value of the D2 agonist [3H]NPA binding sites in the L-hD21/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-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 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.

Original languageEnglish
Pages (from-to)292-299
Number of pages8
JournalMolecular Brain Research
Volume36
Issue number2
DOIs
StatePublished - Mar 1996
Externally publishedYes

Keywords

  • CCK
  • DA D receptors
  • Receptor binding
  • Receptor cDNA transfection
  • Receptor-receptor interaction
  • Receptors

Fingerprint

Dive into the research topics of 'Regulation of dopamine D2 receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCKB and D2L receptor cDNAs'. Together they form a unique fingerprint.

Cite this