Beta-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.
Ho
C L
CL
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Ko
J L
JL
Li
C H
CH
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006168:Guinea Pigs; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D001615:beta-Endorphin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D011957:Receptors, Opioid; D001615:beta-Endorphin; C031261:glutamine-8 beta-endorphin; C033847:beta-endorphin, Trp(27); C058591:beta-endorphin, Tyr(31)