Evaluation of the interactions of mu and delta selective ligands with [3H]D-Ala2-D-Leu5-enkephalin binding to mouse brain membranes.
The interactions of putative mu and delta selective ligands with [3H]D-ala2-D-leu5 enkephalin (DADLE) binding to mouse brain membranes were investigated. Computerized curve fitting of displacement curves performed at three different concentrations of 3H-DADLE indicated that a one site competitive model was sufficient to explain the interactions of leu-enkephalin (LE) and D-ser2-thr6-leucine enkephalin with 3H-DADLE binding. Similar experiments with morphine and morphiceptin were unique in that the multiple displacement curves crossed over one another. A two-site competitive model was required to adequately describe the interactions of these mu selective ligands with 3H-DADLE. This two-site model was one in which the inhibitor had higher affinity for the site labeled with lower affinity by 3H-DADLE. However, this two site model did not correctly predict the interaction of LE with 3H-DADLE in the presence of morphiceptin. These data indicate that: 1) putative mu and delta selective ligands do not bind to a common high affinity site; 2) mu selective ligands are not simple mixed inhibitors of a single site labeled by 3H-DADLE; and 3) competitive binding models may not explain the interaction of mu ligands with 3H-DADLE binding.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003201:Computers; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D008024:Ligands; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine