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Opioid receptor binding characteristics of the non-equilibrium μ antagonist, β-funaltrexamine (β-FNA)

1985; Elsevier BV; Volume: 107; Issue: 3 Linguagem: Inglês

10.1016/0014-2999(85)90257-2

1879-0712

Susan J. Ward, David S. Fries, Dennis L. Larson, Philip S. Portoghese, A.E. Takemori,

Receptor Mechanisms and Signaling

β-Funaltrexamine (β-FNA) bound to mouse brain membranes in a reversible and an irreversible (not removed by washing of the membrane) manner, and a portion of each type of binding was opioid-specific. Addition of 100 mM NaCl to the incubating medium enhanced the binding of β-FNA to membranes. Using membranes preincubated with β-FNA (1 μM) and then washed three times, the maximum number of binding sites available to [3H]morphine was markedly diminished whereas the affinity of morphine for binding sites was not significantly altered. The binding of [3H]naltrexone was also reduced markedly by β-FNA pretreatment. In similarly pretreated membranes, the binding of [3H]methionine enkephalin [3H][D-Ala2,D-Leu5]enkephalin (DADLE) or [3H]ethylketazocine was reduced to a smaller extent. Using brain membranes from mice pretreated with a single subcutaneous injection of β-FNA (100 mg/kg) 48 h prior to use, the binding of [3H]methionine enkephalin was unaffected whereas the number of binding sites available to [3H]morphine was significantly reduced. The inhibition by various ligands of the reversible binding of [3H]β-FNA resembled the relative ability of the same ligands to inhibit the binding of [3H]ethylketazocine. It was concluded that the irreversible portion of the binding of β-FNA demonstrates a selectivity for μ over δ binding sites, and that the reversible portion of the binding of β-FNA demonstrates a selectivity for κ binding sites over μ or δ binding sites. As such, the binding characteristics of β-FNA are consistent with its profile in vivo and in isolated tiussue studies in vitro.