Resolution of Biphasic Binding of the Opioid Antagonist Naltrexone in Brain Membranes |
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Authors: | Ann E Remraers Fedor Medzihradsky |
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Affiliation: | Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606. |
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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. |
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Keywords: | Opioid receptors Agonist-antagonist binding μ- and δ-se- lective opioids [3H] Naltrexone Rat brain cortex |
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