β‐Endorphin: analgesic and receptor binding activity of non‐mammalian homologs

Abstract

Analgesic potencies of turkey, ostrich and des-acetyl salmon .beta.-endorphins were measured in the tail-flick test and binding affinities determined by radioreceptor assay. The duration of analgesia and the slope of the dose-response curves generated by these peptides are similar to those elicited by mammalian .beta.-endorphins. This suggests that they act in vivo and in vitro on the same population of opiate receptors. The ratio of binding to analgesic potencies observed for these peptide varies nearly 6-fold. Structure-activity analysis suggests that a basic side-chain at position 9 is required in order to produce a high opiate activity both in vivo and in vitro. A reexamination of the biological activities of camel .beta.-endorphin shows that the analgesic potency and binding affinity of this peptide are, respectively, 1.7 and 2.7 times higher than human .beta.-endorphin. His-27 and/or Gln-31 may contribute to this increased potency. The dissociation of radioreceptor binding affinity from analgesic potency in these naturally occurring .beta.-endorphin homologs suggests that either the conditions under which the binding assay is performed mask the true binding potency in the brain or that, once bound to the appropriate receptor, these homologs do not possess equal ability to produce biological effects.