Dynorphin uses a non-opioid mechanism to potentiate N-methyl-D-aspartate currents in single rat periaqueductal gray neurons.
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.
Lai
S L
SL
Department of Neurology, Kaohsiung Medical College Hospital, Taiwan.
Gu
Y
Y
Huang
L Y
LY
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D004399:Dynorphins / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000166:cytology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D016202:N-Methylaspartate; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C082245:dynorphin (2-17)