Naloxonazine effects on the interaction of enkephalin analogs with mu- 1, mu and delta opioid binding sites in rat brain membranes

RA Cruciani, RA Lutz, PJ Munson and D Rodbard

The authors have characterized the opioid receptors of rat brain membranes using self- and cross-displacement studies with both tritiated and unlabeled [D-Ala2, D-Leu5]-enkephalin and [D-Ala2, MePhe4, Gly-ol5]-enkephalin. Mathematical modeling demonstrated the presence of three classes of binding sites, corresponding to mu, delta and the putative mu-1 classes of site. Unlabeled naloxonazine shows high affinity for all three classes of sites, with highest affinity for the mu-1 sites. Membranes were preincubated with 50 nM naloxonazine or with controls (50 nM naloxone or buffer) for 30 min. Preincubation of membranes with 50 nM naloxonazine resulted in a dramatic, nearly 2-fold reduction in the binding of [3H][D-Ala2, D-Leu5]-enkephalin and [3H][D- Ala2, MePhe4, Gly-ol5]-enkephalin relative to the controls. Quantitative analyses using mathematical modeling with program "LIGAND" suggested that this effect was primarily "competitive," i.e., attributable to changes in affinity, with no apparent or detectable noncompetitive or irreversible effects on binding capacities for the three classes of sites.

Volume 242, Issue 1, pp. 15-20, 07/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				B. Bontempi and F. R. Sharp Systemic Morphine-Induced Fos Protein in the Rat Striatum and Nucleus Accumbens Is Regulated by µ Opioid Receptors in the Substantia Nigra and Ventral Tegmental Area J. Neurosci., November 1, 1997; 17(21): 8596 - 8612. [Abstract] [Full Text] [PDF]