Binding of kappa- and sigma-opiates in rat brain
Detailed displacements of (/sup 3/H)dihydromorphine by ketocyclazocine and SKF 10,047, (/sup 3/H)ethylketocyclazocine by SKF 10,047, and (/sup 3/H)SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of /sup 3/H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of (/sup 3/H)dihydromorphine (KD . 3 nM), (/sup 3/H)ethylketocyclazocine (KD . 4 nM), (/sup 3/H)SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-(/sup 3/H)enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).
- Research Organization:
- George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York
- OSTI ID:
- 6718664
- Journal Information:
- J. Neurosci.; (United States), Journal Name: J. Neurosci.; (United States) Vol. 2:6; ISSN JNRSD
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
ANALGESICS
ANIMAL TISSUES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BINDING ENERGY
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL ANALYSIS
COMPARATIVE EVALUATIONS
DRUGS
ENDORPHINS
ENERGY
ENKEPHALINS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MORPHINE
NARCOTICS
NERVE TISSUE
NERVOUS SYSTEM
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHYSIOLOGY
POLYPEPTIDES
PROTEINS
QUANTITATIVE CHEMICAL ANALYSIS
QUANTITY RATIO
RATS
RODENTS
TISSUES
TRITIUM COMPOUNDS
VERTEBRATES