Characterization and autoradiographic visualization of (+)-(3H)SKF10,047 binding in rat and mouse brain: further evidence for phencyclidine/sigma opiate receptor commonality

Journal Article · Thu May 01 04:00:00 EDT 1986 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5528647

Sircar, R; Nichtenhauser, R; Ieni, J R; Zukin, S R

The binding specificity of (+)-(/sup 3/H)N-allylnormetazocine, the dextrorotatory isomer of the prototypical sigma opiate SKF10,047, was determined in rat and mouse brain and the neuroanatomical distribution of its binding sites elucidated by quantitative autoradiography in sections of rat brain. Computer-assisted Scatchard analysis revealed an apparent two-site fit of the binding data in both species and in all rat brain regions examined. In whole rat brain, the Kd values were 3.6 and 153 nM and the maximum binding values were 40 fmol and 1.6 pmol/mg of protein for the apparent high- and low-affinity binding sites, respectively. (+)-SKF10,047, haloperidol and pentazocine were among the most potent inhibitors of 7 nM (+)-(/sup 3/H)SKF10,047 binding to the higher affinity sites; rank orders of ligand potencies at these sites differ sharply from those that have been reported for the (/sup 3/H)phencyclidine (PCP) site, or for eliciting PCP-like or SKF10,047-like behaviors. By contrast, rank orders of potency of sigma opiods, PCP derivatives and dioxolanes for displacement of 100 nM (+)-(/sup 3/H)SKF10,047 from the more numerous lower affinity sites in the presence of 100 nM haloperidol agreed closely with their potencies in the (/sup 3/H)PCP binding assay as well as their potencies in exerting PCP- or SKF10,047-like behavioral effects. In order to compare directly the anatomical localizations of PCP and (+)-SKF10,047 binding sites, quantitative light microscopy autoradiography utilizing tritium-labeled PCP and (+)-SKF10,047 was carried out in rat brain sections. (+)-(/sup 3/H)SKF10,047 binding was observed to follow the regional pattern of (3H)PCP binding but also to bind in other regions not associated with PCP receptors.

• Research Organization: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
• OSTI ID: 5528647
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 2; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DRUGS
ENDORPHINS
IN VITRO
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MICE
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TRITIUM COMPOUNDS
VERTEBRATES