Dynorphin1–13: interaction with other opiate ligand bindings in vitro

Dynorphin_1–13 is a potent inhibitor of electrically-induced contractions in the guinea pig ileum, where it has the properties of κ-(ethylketocyclazocine) type opioids. In the brain, however, it has no analgesic potency, yet inhibits that induced by morphine. To gain further insight into its mechanism of action in the latter system, we tested its ability to complete for the binding of several opiates to brain membranes in vitro. Dynorphin_1–13 inhibited the binding of all ligands examined, including dihydromorphine, d-Ala²-d-Leu⁵-enkephalin, ethylketacyclazocine (EKC) and naloxone. In all cases, it reduced the number of high affinity sites and, in the case of EKC, it also increased the K_d. We conclude that the mechanism of dynorphin inhibition is not simple rapidly reversible competition and is certainly not identical with respect to all opiate ligands.