Opioid receptor binding characteristics of the non-equilibrium mu antagonist, beta-funaltrexamine (beta-FNA).
beta-Funaltrexamine (beta-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 beta-FNA to membranes. Using membranes preincubated with beta-FNA (1 microM) 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 beta-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 beta-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] beta-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 beta-FNA demonstrates a selectivity for mu over delta binding sites, and that the reversible portion of the binding of beta-FNA demonstrates a selectivity for kappa binding sites over mu or delta binding sites. As such, the binding characteristics of beta-FNA are consistent with its profile in vivo and in isolated tissue studies in vitro.
Ward
S J
SJ
Fries
D S
DS
Larson
D L
DL
Portoghese
P S
PS
Takemori
A E
AE
D000818:Animals; D001921:Brain / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D009020:Morphine / Q000378:metabolism; D009270:Naloxone / Q000031:analogs & derivatives*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium
D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium; D009270:Naloxone; D004744:Enkephalin, Methionine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine