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• W2004193077 abstract "Chronic infusion of morphine to guinea pigs produced selective changes in mu agonist binding properties in cerebrocortical membrane preparations. Employing the mu-selective opioid agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) in direct binding studies and in competition of labeled antagonist binding, we found that the major changes were a decrease in the number of sites with high affinity for agonist, a small reduction in total receptor number, and a loss in the ability of guanosine 5'-[gamma-thio]triphosphate to regulate binding. A fraction of high-affinity mu receptors appeared to retain their high affinity for agonist and their sensitivity to guanine nucleotide analogue after the induction of morphine tolerance, possibly because the morphine concentrations achieved in brain were insufficient to uncouple all mu receptors from associated guanine nucleotide-binding regulatory proteins. Some membrane preparations were treated with pertussis toxin, which has been shown to functionally uncouple mu opioid receptors from their effector systems. In these preparations, a single agonist-affinity state of the receptor was observed. The apparent dissociation constant for this affinity state in pertussis toxin-treated membranes was similar to the lower-affinity state observed in preparations from morphine-tolerant animals. In contrast to the changes observed at mu opioid binding sites, no significant changes in agonist affinity or binding density were observed for selective delta or kappa agonists, consistent with the development of selective tolerance at mu receptors." @default.
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• W2004193077 date "1989-08-01" @default.
• W2004193077 modified "2023-10-16" @default.
• W2004193077 title "Selective changes in mu opioid receptor properties induced by chronic morphine exposure." @default.
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• W2004193077 doi "https://doi.org/10.1073/pnas.86.16.6393" @default.
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