The inhibitory opioid activities of beta-h-endorphin (beta-h-EP), its structurally related peptide analogues [Gln8, Gly31]-beta-h-EP-Gly-Gly-NH2 (Gly-Gly-beta-h-EP), [Arg9,19,24,28,29]-beta-h-EP (Arg-beta-h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta-h-EP, beta-h-EP and Gly-Gly-beta-h-EP. Neither Gly-Gly-beta-h-EP nor Arg-beta-h-EP antagonized the inhibitory action of beta-h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta-h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta-h-EP and Arg-beta-h-EP, it was only about 3-fold for Gly-Gly-beta-h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta-h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.
