Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action.
Opiate alkaloid and opioid peptide actions on spontaneous neuronal activity and postsynaptic amino acid responsiveness were assessed using intracellular recording techniques applied to murine spinal cord neurons in primary dissociated cell culture. Application of opiates was by superfusion and amino acids by iontophoresis. Glycine and GABA but not glutamate responses were antagonized by the opiate alkaloids. Since opiate effects on glycine and GABA responses were not naloxone-reversible, only weakly stereospecific, and not produced by the opioid peptide [D-Ala2]-Met-enkephalinamide, it is unlikely that these effects were mediated by opiate receptors. Opiate depression of glycine inhibition was correlated with the induction of paroxysmal depolarizations in cultured spinal cord neurons, suggesting that antagonism of inhibitory amino acid transmission may underlie the convulsant actions of high concentrations of the opiate alkaloids.
D000818:Animals; D002478:Cells, Cultured; D003917:Dextrorphan / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology*; D007981:Levorphanol / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013116:Spinal Cord / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D004745:Enkephalins; D009294:Narcotics; D003917:Dextrorphan; D007981:Levorphanol; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D009020:Morphine; D005998:Glycine