Abstract
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.
MeSH terms
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Animals
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Binding Sites / physiology
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Binding, Competitive / physiology
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism*
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Dopamine / deficiency
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Dynorphins / metabolism*
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Dynorphins / pharmacology
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Excitatory Amino Acid Agonists / metabolism
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Excitatory Amino Acid Antagonists / metabolism
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Glycine / metabolism*
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Male
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Glycine / drug effects
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Receptors, Glycine / metabolism
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Glrb protein, rat
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate
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Dynorphins
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Glycine
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Dopamine