Characterization of membrane-bound and soluble D2 receptors in canine caudate using ( sup 125 I)IBZM
- Univ. of Pennsylvania School of Medicine, Philadelphia (USA)
(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl) methyl)benzamide (IBZM) was shown to be a high-affinity antagonist selective for the D2 subtype of dopamine receptor. Binding sites for the radioligand (125I)IBZM were characterized with membranes and digitonin-solubilized extracts of canine caudate enriched by chromatography on heparin-agarose. Nonspecific binding, defined using 2 microM (+)-butaclamol, was less than 10% of the total ligand bound at the Kd of the receptor for ({sup 125}I)IBZM. Direct binding, competition and kinetic experiments indicated that ({sup 125}I)IBZM bound to a homogeneous population of binding sites. The rank order of potency for inhibition of the binding of ({sup 125}I)IBZM by antagonists and agonists was found to be consistent with the pharmacological profile expected of a D2 receptor. The affinities of ({sup 125}I)IBZM for membrane-associated and detergent-solubilized binding sites were essentially identical (Kd congruent to 0.4 nM). This result contrasts with findings obtained in studies with ({sup 3}H)spiroperidol, where a marked decrease in the affinity of the receptor for the ligand has been observed during detergent solubilization and purification of the receptor. The high selectivity, nanomolar affinity and high specific activity of ({sup 125}I)IBZM and the results obtained in studies with detergent extracts suggest that ({sup 125}I)IBZM will be a particularly useful ligand for studies of D2 receptors in the presence of detergents.
- OSTI ID:
- 5564505
- Journal Information:
- Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 250:1; ISSN JPETA; ISSN 0022-3565
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADDITIVES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL COMPOSITION
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DETERGENTS
DOGS
DOPAMINE
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMULSIFIERS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
PYRROLES
PYRROLIDINES
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
SURFACTANTS
SYMPATHOLYTICS
SYMPATHOMIMETICS
TRACER TECHNIQUES
VERTEBRATES
WETTING AGENTS