Is There a Common, High-Affinity Opioid Binding Site in Rat Brain?

Abstract

At low concentrations, 3H-naloxone apparently bound to two sites, of high (K_D 0.50nM) and low (K_D 2.0nM) affinity. Binding to the high affinity site was preferentially blocked by naloxonazine. This is consistent with the high and low affnity sites representing the μ₁ and μ₂ sites respectively. Binding of 3H-naloxone to the μ₁ and μ₂ sites was differentially inhibited by opioids. Compared to u₂ binding, DADLE and DAGO preferentially inhibited μ₁ binding. DADLE inhibited the binding of 3H-DAGO potently and in a competitive manner. DAGO inhibited the binding of 3H-DADLE from two sites for which DAGO had high and low affinities. Scatchard analysis indicated that both 3H-DAGO and 3H-DADLE bound to one class of sites, with 3H-DADLE having a 2–3 fold greater Bmax.

It is concluded that 3H-opioids bind to at least three sites—μ₁, μ₂ and δ. The μ₁ site represents a high affinity binding site for both opioid peptides and opioid alkaloids. DAGO is a selective ligand for the μ₁ site, whilst DADLE interacts with μ₁ and δ sites with similar affinities.