β-Endorphin: receptor binding and peripheral opioid activities of [Gln8]-, [Trp27]-, and [Tyr31]-analogs

Three beta h-EP analogs which show different extents of alteration in analgesic potency by substitution of a single amino acid residue were assayed for their peripheral opioid activity and the binding to opioid mu-receptor to determine the relationships among the opioid activities obtained from different assays. In the guinea pig ileum assay, [Gln8]-beta h-EP showed a higher inhibitory activity than the parent peptide, [Tyr31]-analog had the same potency as beta h-EP, while [Trp27]-analog retained only one fourth the potency of beta h-EP. Assayed on the vas deferens of the mouse and the rat, all three substituted beta h-EP analogs exhibited a lower potency than their parent peptide. Receptor binding assay using [3H]-dihydromorphine as the primary ligand showed that [Gln8]-analog had a binding potency 1.5-fold that of beta h-EP, while the potencies of [Tyr31]- and [Trp27]-analogs were not significantly different from that of the parent peptide. No correlation in relative potency was found between vas deferens assays and their mu-receptor binding or analgesic activity. However, the relative potencies of binding to mu-receptor in [Gln8]- and [Tyr31]-analogs were found to be consistent with those of analgesic and guinea pig ileum assays, whereas the binding to beta-EP receptor of all analogs appeared to be related to the charge properties of beta-EP molecule.