Dopamine-induced reduction in the density of guanine nucleotide-sensitive D1 receptors in human postmortem brain in the absence of apparent D1:D2 interactions

• Published in: Neuropharmacology 1995-07, Vol.34 (7), p.777-783
• Main Authors: MCCAULEY, P. G, O'BOYLE, K. M, WADDINGTON, J. L
• Format: Article
• Language: English
• Subjects: Autopsy; Benzazepines - pharmacology; Binding, Competitive; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Caudate Nucleus - drug effects; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Guanine Nucleotides - pharmacology; Humans; Male; Middle Aged; Nucleus Accumbens - drug effects; Putamen - drug effects; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D1 - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(95)00039-9

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.