title: Coactivation of dopamine D1 and D2 receptors increases the affinity of cholecystokinin-8 receptors in membranes from post-mortem human caudate-putamen.
abstract: The effects of dopamine in vitro were investigated on the binding sites for cholecystokinin-8 (sulphated, CCK-8) and neurotensin in membrane preparations of the caudate-putamen and nucleus accumbens of post-mortem human brains. Dopamine reduced the IC50 value of competition curves with CCK-8 for [125I]CCK-8 binding in membranes from the caudate-putamen, but not the nucleus accumbens, with a maximal decrease of -25 +/- 9% at 300 nM of dopamine. This decrease could be antagonized by 100 nM of SCH 23390 or 100 nM of raclopride. Kinetic analysis of [125I]CCK-8 binding showed a decrease in the first order dissociation rate constant and in the kinetic Kd (-22 +/- 6% and -24 +/- 6%, respectively) at 300 nM of dopamine, without any significant effect on the apparent or actual association rate constant. Competition curves with neurotensin versus [125I]neurotensin were not affected by dopamine (10-1000 nM) in membranes from the caudate-putamen or the nucleus accumbens. These results suggest that dopamine, by synergistic stimulation of both D1 and D2 receptors, selectively increases the affinity of CCK-8 receptors in the human caudate-putamen, by a selective inhibition of ligand dissociation. This increase may reflect a positive feed-back mechanism, further enhancing the modulatory effects of CCK-8 on dopamine neurotransmission.
authors.affiliation: Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: von Euler
authors.forename: P
authors.initials: P
authors.lastname: Mailleux
authors.forename: M
authors.initials: M
authors.lastname: von Euler
authors.forename: S N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: J J
authors.initials: JJ
authors.lastname: Vanderhaeghen
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D002421:Caudate Nucleus / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism
chemical_list: D018492:Dopamine Antagonists; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter