Dopamine-induced reduction in the density of guanine nucleotide-sensitive D1 receptors in human postmortem brain in the absence of apparent D1: D2 interactions.
The effects of dopamine and guanine nucleotides on the binding of the D1 dopamine receptor antagonist ligand [3H]SCH 23390 were examined in membranes prepared from putamen, caudate and nucleus accumbens of human postmortem brain. Dopamine induced a concentration-dependent decrease in the apparent maximum number of binding sites (Bmax) in each brain region studied, and displaced binding in a biphasic manner consistent with the presence of both high and low affinity states of the D1 receptor; the GTP analogue Gpp(NH)p transformed this biphasic displacement to a monophasic pattern consistent with a shift of high affinity sites to a low affinity state. However, the selective D2 antagonist eticlopride did not reverse the action of dopamine to decrease Bmax. These data suggest that dopamine decreases Bmax for D1 receptors through a high affinity, guanine nucleotide-sensitive agonist binding site, but fail to reveal D1:D2 interactions at this synaptic level.
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
P G
PG
McCauley
K M
KM
O'Boyle
J L
JL
Waddington
D001344:Autopsy; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000187:drug effects; D011699:Putamen / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology*
D001552:Benzazepines; D006150:Guanine Nucleotides; D017447:Receptors, Dopamine D1; D004298:Dopamine