PHARMACOLOGICAL CHARACTERIZATION OF THE EPSILON-OPIATE RECEPTOR

Abstract

The .epsilon.-opiate receptor of the electrically stimulated rat vas deferens was characterized by means of .beta.-endorphin, its fragments and derivatives thereof [.gamma.-endorphin, [Des-Tyr1]-.beta.-endorphin, methionine-enkephalin, [D-Ala2]-.beta.-endorphin, [L-Leu5]-.beta.-endorphin, N-acetyl-.beta.-endorphin [D-Ala2,MePhe4]-.beta.-endorphin, .beta.-endorphin 18-31, etorphine, MR 2034 (5,9-dimethyl-2''-hydroxy-2-tetrahydrofurfuryl-6,7 benzomorphan), and sufentanyl] and by its tolerance development. Evidence for the uniqueness of the .epsilon.-receptor as compared to .mu.- and .delta.-receptors of the guinea-pig ileum and the mouse vas deferens, respectively, was presented. It appears that an activation of the .epsilon.-receptor requires at least the .beta.-endorphin sequence 1-21, which sharply contrasts with the relatively high sensitivity of .mu.- and .delta.-receptors to much shorter fragments of this opioid peptide. After chronic exposure of rats to etorphine, the isolated vas deferens shows a dramatic loss of sensitivity to .mu.-receptor agonists, but only a moderate decrease in sensitivity to .beta.-endorphin.