Etorphine binds to multiple opiate receptors of the caudate nucleus with equal affinity but with different kinetics

AM Tolkovsky

The binding of [3H]etorphine, a potent opiate agonist of the oripavine series, to membranes derived from sheep brain caudate nucleus is analyzed. Although the receptors are saturated by [3H]etorphine in a homogeneous fashion with an apparent dissociation constant of 1.16 +/- 0.3 nM, kinetic displacement studies reveal that at least two classes of sites are involved. All of the specific sites for [3H]etorphine are blocked by morphine or naloxone if these ligands are added prior to, or simultaneously with [3H]etorphine. Otherwise, when [3H]etorphine is added prior to morphine or naloxone, only one-third of the specific binding can be effectively displaced. The difference in the displacement patterns between the two classes of sites can be accounted for by the kinetics of the interaction between [3H]etorphine and the receptors. At 37 degrees [3H]etorphine dissociates from one-third of the sites with a half-life of 2.3 min and from the remaining sites with a half-life of 70 min. The sites which release [3H]etorphine slowly have a 10-fold higher apparent affinity for morphine and for naloxone as compared with the more rapidly reversible sites. The binding data are only partially compatible with a model which involves two independent classes of sites. The possibility of identifying the site from which [3H]etorphine dissociates slowly with millimicron, delta, or kappa opiate receptors is explored in light of the fact that [3H]etorphine is a mixture of D- and L-stereoisomers.

Volume 22, Issue 3, pp. 648-656, 11/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				P. J. Woolf and J. J. Linderman Untangling Ligand Induced Activation and Desensitization of G-Protein-Coupled Receptors Biophys. J., January 1, 2003; 84(1): 3 - 13. [Abstract] [Full Text] [PDF]

				AllanD. Blake, G. Bot, JohnC. Freeman, and T. Reisine Differential Opioid Agonist Regulation of the MouseµOpioid Receptor J. Biol. Chem., January 10, 1997; 272(2): 782 - 790. [Abstract] [Full Text] [PDF]