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Resolution of Biphasic Binding of the Opioid Antagonist Naltrexone in Brain Membranes
Author(s) -
Remraers Ann E.,
Medzihradsky Fedor
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08288.x
Subject(s) - naltrexone , antagonist , opioid antagonist , membrane , chemistry , opioid , pharmacology , neuroscience , psychology , (+) naloxone , medicine , receptor , biochemistry
In synaptosomal membranes from rat brain cortex, in the presence of 150 m M NaC1, the opioid antagonist [ 3 H] naltrexone bound to two populations of receptor sites with affinities of 0.27 and 4.3 n M , 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 [ 3 H] naltrexone. As shown by nonlinear least‐squares analysis, the μ opioids Tyr‐D‐Ala‐Gly‐(Me)Phe‐Gly‐ol or sufentanil abolished high‐affinity [ 3 H] naltrexone binding, whereas the δ‐selective ligands [D‐ Pen 2 , D‐Pen 5 ] 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.