Dynorphin displaces binding at the glycine site of the NMDA receptor in the rat striatum

Binding of dynorphin A (1–17 and 2–17) to NMDA receptors in the rat striatum was studied by displacing radioactive ligands for the receptor's polyamine ([3H]-Ifenprodil), glutamate ([3H]-CGP-39653), dizocilpine ([3H]-MK-801) and glycine ([3H]-MDL105,519) sites with the neuropeptide. Dynorphin A selectively displaced [3H]-MDL105,519 and none of the other ligands. Opioid antagonists did not affect displacement. Thus, in the striatum dynorphin may regulate NMDA receptor function via the glycineB site through non-opioid mechanisms. This may contribute to the long-term changes in behavioral responsiveness seen after dopamine depletion and treatment with dopaminomimetics which are associated with substantial changes in striatal dynorphin metabolism.