Dynorphin_1–8 and dynorphin_1–9 are ligands for the κ-subtype of opiate receptor

Abstract

It is generally accepted that there are three subtypes of opiate receptor: µ, δ and κ. The main endogenous ligands for the µ-and δ-sites are Met⁵-enkephalin, Leu⁵-enkephalin and β-endorphin, whereas the putative endogenous ligands for the κ-binding site were unknown until recent observations suggested that dynorphin_1–13 might be a candidate. The most convincing evidence for this view has been presented by Goldstein and his colleagues who showed that dynorphin_1–13 is a specific endogenous ligand for the κ-receptor and has a high potency and long duration of action^1–13. We show here that the sequences Leu⁵-enkephalyl-Arg-Arg-Ile (dynorphin_1–8) and, particularly, Leu⁵-enkephalyl-Arg-Arg-Ile-Arg (dynorphin_1–9) are selective ligands for the κ-binding site. Whereas dynorphin_1–13 and dynorphin_1–17 are relatively resistant to the action of peptidase and have a long duration of action in vitro after wash-out, dynorphin_1–8 and dynorphin_1–9 are readily degraded by peptidases and their duration of action is much shorter. For this and other reasons, the possibility will have to be considered that dynorphin_1–8 or dynorphin_1–9 may be transmitters or modulators at the κ-binding site while dynorphin_1–13 and dynorphin_1–17 may act hormonally, that is, at a distance from the site of release.