Link between D sub 1 and D sub 2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86:24
• Main Authors: Seeman, P., Niznik, H.B., Guan, H.C., Booth, G., Ulpian, C.
• Format: Journal Article
• Language: English
• Published: United States 01-12-1989
• Subjects: 550201 - Biochemistry- Tracer Techniques; AMINES; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; AZAARENES; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BODY; CARDIOTONICS; CARDIOVASCULAR AGENTS; DAYS LIVING RADIOISOTOPES; DISEASES; DOPAMINE; DOSE-RESPONSE RELATIONSHIPS; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE GLANDS; GLANDS; GUANINE; HEREDITARY DISEASES; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; LIGANDS; MEMBRANE PROTEINS; MOLECULAR STRUCTURE; NERVOUS SYSTEM DISEASES; NEUROREGULATORS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PHARMACOLOGY; PHENOLS; PITUITARY GLAND; POLYPHENOLS; PROTEINS; PURINES; RADIOISOTOPES; RADIORECEPTOR ASSAY; RECEPTORS; SYMPATHOMIMETICS; TRACER TECHNIQUES; TRITIUM COMPOUNDS
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.24.10156

Dopamine receptor types D{sub 1} and D{sub 2} can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D{sub 1}-D{sub 2} interaction in homogenized tissue as revealed by ligand binding. D{sub 2} agonists lowered the binding of ({sup 3}H)raclopride to D{sub 2} receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D{sub 1}-selective antagonist SCH 23390 prevented the agonist-induced decrease in ({sup 3}H)raclopride binding to D{sub 2} sites in the striatum but not in the anterior pituitary, which has no D{sub 1} receptors. Conversely, a dopamine-induced reduction in the binding of ({sup 3}H)SCH 23390 to D{sub 1} receptors could be prevented by the D{sub 2}-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D{sub 1}-D{sub 2} interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D{sub 2} receptors in the high-affinity state. Thus, the D{sub 1}-D{sub 2} link may be mediated by guanine nucleotide-binding protein components. The link may underlie D{sub 1}-D{sub 2} interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.