Characterization of specific binding sites for (/sup 3/H)(d)-N-allylnormetazocine in rat brain membranes

Journal Article · Tue Jan 01 04:00:00 EST 1985 · Mol. Pharmacol.; (United States)

OSTI ID:5666181

Itzhak, Y; Hiller, J M; Simon, E J

Binding of (/sup 3/H)(d)-N-allylnormetazocine ((/sup 3/H)(d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax . 260 fmol/mg of protein) and manifests moderately high affinity (Kd . 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for (/sup 3/H)(d)-NANM-binding sites is as follows: (d)-NANM . PCP-3-OH greater than (d)-cyclazocine greater than N-ethylphenylcyclohexylamine greater than PCP greater than (l)-cyclazocine . dextrorphan greater than (d/l)-ethylketocyclazocine greater than (d/l)-bremazocine greater than (1)-NANM greater than 1-phenylcyclohexylamine greater than levorphanol. Other opioid ligands, relatively selective for each of the types of opioid binding sites other than sigma, such as morphine (mu), H-Tyr-D-Ala(Me)Phe-NH-CH2-OH (mu), D-Ala2-D-Leu5-enkephalin (delta), tifluadom (kappa), and U 50488 (kappa) as well as etorphine and naloxone were all unable to compete with (/sup 3/H)(d)-NANM for specific binding even at a concentration of 1 microM. Regional distribution studies of (/sup 3/H)(d)-NANM-binding sites show high density in the hippocampus, thalamus, hypothalamus, and amygdala and low density in cerebellum and nonfrontal neocortex membranes of the rat brain. These binding sites are very sensitive to protein-modifying enzymes and reagents such as trypsin and N-ethylmaleimide and to heat denaturation. These results provide direct biochemical evidence for the existence of distinct (d)-NANM-binding sites in rat brain.

• Research Organization: New York Univ. Medical Center, NY
• OSTI ID: 5666181
• Journal Information: Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 27:1; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALOIDS
ANALGESICS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMISTRY
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL BONDS
CHEMISTRY
COMPARATIVE EVALUATIONS
DENSITY
DISTRIBUTION
DRUGS
ENDORPHINS
ENKEPHALINS
HIPPOCAMPUS
HYPOTHALAMUS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANES
MORPHINE
NARCOTICS
NERVOUS SYSTEM
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHYSICAL PROPERTIES
POLYPEPTIDES
PROTEINS
RATS
RODENTS
THALAMUS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES