Stereospecific binding of 3H-phencyclidine in brain membranes.
Phencyclidine (PCP) displaceable binding of 3H-PCP to glass-fiber filters was eliminated and total binding markedly reduced by initial treatment of the discs with 0.05% polyethyleneimine. Assessed with treated filters, unlabeled PCP displaced 3H-PCP in both rat and pigeon brain membranes with an EC50 of 1 microM. Of similar high inhibitory potency were dextrorphan, levorphanol, SKF 10047 and ketamine, while morphine, naloxone and etorphine had EC50 values higher then 1 mM. Using the dissociative anesthetic dexoxadrol and its inactive isomer levoxadrol as displacing agents, stereospecific binding of 3H-PCP was obtained in rat and pigeon brain membranes. The markedly higher potency of dexoxadrol, relative to levoxadrol, in displacing bound 3H-PCP is compatible with behavioral data for these enantiomers. However, they were equipotent in displacing 3H-PCP bound to glass-fiber filters in the absence of tissue. Heat denaturation, but not freezing, abolished stereospecific binding of 3H-PCP, which was also absent in rat liver membranes. The stereospecific binding component in brain displayed biphasic saturability at 60-70 nM and 300-400 nM, respectively.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D010856:Columbidae; D005374:Filtration / Q000379:methods; D005898:Glass; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism*; D011094:Polyethyleneimine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009292:Narcotic Antagonists; D009294:Narcotics; D011094:Polyethyleneimine; D010622:Phencyclidine