Dopaminergic 3H-agonist receptors in rat brain: new evidence on localization and pharmacology
Recent methodological advances have allowed the reliable assay of specific dopaminergic 3H-agonist binding sites in rat striatum. Lesions of dopamine(DA) terminals or drugs which deplete DA levels prevent the preincubation-induced increase in binding, and this effect is completely reversible by preincubation with added DA. It is concluded that the evidence supporting the existence of presynaptic D-3 sites is artefactual and that 3H-DA binding sites are more likely related to post-synaptic receptors. 3H-DA binding involves two sites, one of which has pharmacologic properties similar to D-1 receptors, whereas the other resembles D-2 receptors. The affinity of 15 antipsychotic drugs for 3H-haloperidol binding sites was highly correlated (R = 0.94) with their inhibitory potency at a subset of 3H-DA binding sites. However, the inhibition of 3H-DA binding by antipsychotic drugs was noncompetitive. These findings can be explained by an allosteric model, whereby antagonists bind to a site different from but allosterically linked to a high-affinity 3H-DA binding site.
- Research Organization:
- Pfizer Central Research, Groton, CT
- OSTI ID:
- 6354722
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 34:4; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DOPAMINE
DRUGS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHARMACOLOGY
PHENOLS
POLYPHENOLS
RADIOASSAY
RATS
RECEPTORS
RODENTS
SYMPATHOMIMETICS
TRITIUM COMPOUNDS
VERTEBRATES