Allosteric coupling between morphine and enkephalin receptors in vitro.
In a recent paper from our laboratory [Mol. Pharmacol 21:538-547 (1982)] evidence was presented which suggested that [3H]leucine enkephalin labels a single class of binding sites (the enkephalin receptor) and that morphine allosterically induces a masking of enkephalin receptors as a consequence of binding to a receptor (the morphine receptor) not labeled by the 3H-peptide. Evidence is presented in this paper that [3H]etorphine can be used to label selectively the morphine receptor and that the inhibitory dissociation constants (KI) of morphine, etorphine, and human beta-endorphin for the [3H]etorphine binding site closely approximate the concentration of these drugs which produce a half-maximal decrease in the number of enkephalin receptors. Furthermore, an examination of the interaction of leucine enkephalin and methionine enkephalin with the morphine receptor has demonstrated that the pentapeptides are not competitive inhibitors of [3H] etorphine binding, and that they have much lower affinities for the morphine receptor than previously thought. On the basis of these data, a working hypothesis has been formulated which postulates that distinct morphine and enkephalin receptors coexist in an opioid-receptor complex.
D000495:Allosteric Site / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D004723:Endorphins / Q000378:metabolism; D005048:Etorphine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D009020:Morphine / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D001615:beta-Endorphin
D004723:Endorphins; D011957:Receptors, Opioid; D005048:Etorphine; D001615:beta-Endorphin; D009020:Morphine