Pharmacological characterization of the inhibitory activity of βh-endorphin (βh-EP),[Arg9,19,24,28,29]-)βh-EP,[Gln8,Gly31]-βh-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens

Abstract

Abstract The inhibitory opioid activities of βh-endorphin (βh-EP), its structurally related peptide analogues [Gln8, Gly31]-βh-EP-Gly-Gly-NH2 (Gly-Gly-βh-EP), [Arg9,19,24,28,29]-βh-EP (Arg-βh-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-βh-EP, βh-EP and Gly-Gly-βh-EP. Neither Gly-Gly-βh-EP nor Arg-βh-EP antagonized the inhibitory action of βh-EP or methionine enkephalin. An hour of tissue exposure to 30 Nm β-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of βh-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for βh-EP and Arg-βh-EP, it was only about 3-fold for Gly-Gly-βh-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 βh-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.