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.
Voorn
Pieter
P
Department of Anatomy and Neurosciences, ICEN, Vrije Universiteit Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. p.voorn@vumc.nl
van de Witte
Serge Valery
SV
Li
Ka wan
Kw
Jonker
Allert Jan
AJ
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency; D004399:Dynorphins / Q000378:metabolism* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C491948:Glrb protein, rat; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D004399:Dynorphins; D005998:Glycine; D004298:Dopamine