title: Resolution of biphasic binding of the opioid antagonist naltrexone in brain membranes.
abstract: In synaptosomal membranes from rat brain cortex, in the presence of 150 mM NaCl, the opioid antagonist [3H]naltrexone bound to two populations of receptor sites with affinities of 0.27 and 4.3 nM, respectively. Guanosine-5'-(3-thiotriphosphate) had little modulating effect and did not alter the biphasic nature of ligand binding. On the other hand, receptor-selective opioids differentially inhibited the two binding components of [3H]naltrexone. As shown by nonlinear least-squares analysis, the mu opioids Tyr-D-Ala-Gly-(Me)Phe-Gly-ol or sufentanil abolished high-affinity [3H]naltrexone binding, whereas the delta-selective ligands [D-Pen2,D-Pen5]enkephalin, ICI 174,864, and oxymorphindole inhibited and eventually eliminated the low-affinity component in a concentration-dependent manner. These results indicate that, in contrast to the guanine nucleotide-sensitive biphasic binding of opioid-alkaloid agonists, the heterogeneity of naltrexone binding in brain membranes reflects ligand interaction with different opioid-receptor types.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.
authors.forename: A E
authors.initials: AE
authors.lastname: Remmers
authors.forename: F
authors.initials: F
authors.lastname: Medzihradsky
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008566:Membranes / Q000378:metabolism; D009271:Naltrexone / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D004723:Endorphins; D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine