Striatal binding of 2-amino-6,7-(/sup 3/H)dihydroxy-1,2,3,4-tetrahydronaphthalene to two dopaminergic sites distinguished by their low and high affinity for neuroleptics

Journal Article · Thu Jul 01 04:00:00 EDT 1982 · J. Neurosci.; (United States)

OSTI ID:6706234

List, S J; Wreggett, K A; Seeman, P

In order to develop more selective methods for labeling brain dopamine receptors, this study describes in detail the properties of 2-amino-6,7,-(/sup 3/H)dihydroxy-1,2,3,4,-tetrahydronaphthalene ((/sup 3/H) ADTN) binding to dopaminergic sites in rat, calf, and human brain. (/sup 3/H)ADTN labeled two distinct types of dopaminergic binding sites in the brain striatum of the rat, calf, and human. Very low concentrations of dopamine and dopaminergic catecholamines (with IC50 values of 1 to 10 nM) inhibited the binding of (/sup 3/H)ADTN to both sites. Neuroleptics, however, inhibited the binding of (/sup 3/H)ADTN in two distinctly separate concentration ranges, with IC50 values of 0.15 to 40 nM at one site and 100 and 50,000 nM at the other site. The site with high affinity for dopamine and low affinity for neuroleptics had binding properties that corresponded to those of the previously characterized D3 site). The (/sup 3/H)ADTN binding site with high affinity for neuroleptics demonstrated binding characteristics similar to a site labeled by /sup 3/H-Neuroleptics. (/sup 3/H)Apomorphine appeared to label the same two sites as (/sup 3/H)ADTN, while (/sub 3/H)dopamine labeled only the D3 site. Scatchard analysis of (/sup 3/H)ADTN or (/sub 3/H)apomorphine binding, under conditions for selective labeling of the low affinity neuroleptic site (D3) and the high affinity site for neuroleptics, detected a density of 70 fmol/mg of protein for each. The density of the D3 site in the calf striatum (170 fmol/mg of protein) was much greater than that of the high affinity neuroleptic site (50 fmol/mg). In the rat, the dissociation constant (KD) of (/sup 3/H)ADTN was 2 nM for both sites. (/sup 3/H)Apomorphine, however, had a higher affinity for the D3 site (KD.1.6 nM) than for the high affinity neuroleptic site (KD.4.2 nM).

• Research Organization: Department of Pharmacology, University of Toronto, Ontario, Canada
• OSTI ID: 6706234
• Journal Information: J. Neurosci.; (United States), Journal Name: J. Neurosci.; (United States) Vol. 2:7; ISSN JNRSD
• Country of Publication: United States
• Language: English

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550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CALVES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CATTLE
CENTRAL NERVOUS SYSTEM
DOMESTIC ANIMALS
DOPAMINE
DRUGS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
PHYSIOLOGY
POLYPHENOLS
PRIMATES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
RUMINANTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES