Is there a common, high-affinity opioid binding site in rat brain?
At low concentrations, 3H-naloxone apparently bound to two sites, of high (KD 0.50 nM) and low (KD 2.0 nM) affinity. Binding to the high affinity site was preferentially blocked by naloxonazine. This is consistent with the high and low affinity sites representing the mu 1 and mu 2 sites respectively. Binding of 3H-naloxone to the mu 1 and mu 2 sites was differentially inhibited by opioids. Compared to mu 2 binding, DADLE and DAGO preferentially inhibited mu 1 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--mu 1, mu 2 and delta. The mu 1 site represents a high affinity binding site for both opioid peptides and opioid alkaloids. DAGO is a selective ligand for the mu 1 site, whilst DADLE interacts with mu 1 and delta sites with similar affinities.
D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry; D002047:Buprenorphine / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000378:metabolism; D010423:Pentazocine / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D002047:Buprenorphine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D004090:Dihydromorphine; D010423:Pentazocine