Comparison of dopamine receptor sites labeled by (/sup 3/H)-S-sulpiride and (/sup 3/H)-spiperone in striatum

Journal Article · Wed Nov 30 23:00:00 EST 1983 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6541754

Zahniser, N R; Dubocovich, M L

Binding of the radiolabeled active isomer of the neuroleptic sulpiride, (/sup 3/H)-S-sulpiride, to rat and rabbit striatal membranes was characterized. Regardless of whether the specific binding of (/sup 3/H)-S-sulpiride was defined with spiperone or the active isomers of butaclamol or flupenthixol, a single homogeneous++ population of binding sites (rat: Kd . 5.6 nM, maximum binding . 590 fmol/mg of protein; rabbit: Kd . 8.3 nM, maximum binding . 540 fmol/mg of protein) was detected. The pharmacological profile of these sites was characteristic of that described for the dopaminergic D-2 receptor subtype. To determine whether (/sup 3/H)-S-sulpiride and (/sup 3/H)spiperone label common sites in the striatum, the binding of these two radioligands was compared under similar assay conditions. When specific binding of (/sup 3/H)spiperone was defined with S-sulpiride, (/sup 3/H)spiperone labeled the same number of binding sites as (/sup 3/H)-S-sulpiride despite the fact that the affinity of the sites for (/sup 3/H)spiperone was 80- to 90-fold higher than for (/sup 3/H)-S-sulpiride. When specific binding of (/sup 3/H)spiperone was defined with either (+)-butaclamol or (alpha)-flupenthixol, however, approximately 30% more sites were labeled. The predominant site labeled by (/sup 3/H)spiperone also possessed the characteristics of the D-2 receptor. It is concluded that (/sup 3/H)-S-sulpiride under the conditions used is a selective radioligand with which dopamine receptors of the D-2 subtype can be directly measured and localized. (/sup 3/H)Spiperone can be used to detect the same sites only if specific binding is defined with S-sulpiride.

• Research Organization: Univ. of Colorado School of Medicine, Denver
• OSTI ID: 6541754
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 227:3; ISSN JPETA
• 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
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
DOPAMINE
DRUGS
ENZYMES
HYDROXY COMPOUNDS
ISOMERASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
MOLECULAR BIOLOGY
NEUROREGULATORS
ORGANIC COMPOUNDS
PHARMACOLOGY
PHENOLS
POLYPHENOLS
PROTEINS
RABBITS
RATS
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES