Abstract
The interaction of the endogenous K-opioid, dynorphin, with N-methyl-D-aspartate (NMDA) receptors was studied in single periaqueductal gray (PAG) cells using the whole cell patch recording technique. We have found that dynorphin A (1-17) rapidly and reversibly potentiates NMDA-activated currents in a subpopulation of PAG cells. The potentiation cannot be blocked by the non-specific opioid antagonist, naloxone, nor can it be reversed by the specific kappa-opioid antagonist, nor-BNI. In addition, the non-opioid fragment of dynorphin, dynorphin A (2-17), is effective in potentiating NMDA currents, while the specific kappa-opioid, U50,488, cannot mimic the action of dynorphin A (1-17). The non-opioid dynorphin action and the rapid onset and recovery of the potentiation are consistent with the idea that dynorphin interacts directly with NMDA receptors in PAG cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
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Action Potentials / drug effects
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Analgesics, Non-Narcotic / pharmacology
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Animals
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Drug Synergism
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Dynorphins / pharmacology*
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N-Methylaspartate / pharmacology*
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Naloxone / pharmacology
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Neurons / drug effects*
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Neurons / physiology
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Patch-Clamp Techniques
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Peptide Fragments / pharmacology
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Periaqueductal Gray / cytology*
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Rats
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, N-Methyl-D-Aspartate / physiology
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Receptors, Opioid, kappa / drug effects
Substances
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Analgesics, Non-Narcotic
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Narcotic Antagonists
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Peptide Fragments
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Receptors, N-Methyl-D-Aspartate
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Receptors, Opioid, kappa
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Naloxone
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norbinaltorphimine
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Naltrexone
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N-Methylaspartate
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Dynorphins
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dynorphin (2-17)