Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid.
mu opioids, such as morphine and certain enkephalin analogs, are known to modulate glutamate-evoked activity in dorsal horn neurons in the spinal cord and caudal brain stem. Yet the molecular mechanism by which this modulation occurs is not understood. We examined the interactions between glutamate and a selective mu opioid receptor agonist, D-Ala2-MePhe4-Gly-ol5-enkephalin (DAGO), in spinal trigeminal neurons in thin medullary slices of rats. DAGO caused a sustained increase in glutamate-activated currents that are mediated by N-methyl-D-aspartate receptors. Intracellularly applied protein kinase C (PKC) mimics the effect of DAGO, and a specific PKC inhibitor interrupts the sustained potentiation produced by DAGO. Thus, PKC plays a key role in mediating the action of mu opioid peptides.
Chen
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Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77550.
Huang
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LY
D000818:Animals; D004723:Endorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid; D008526:Medulla Oblongata / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D004723:Endorphins; D004745:Enkephalins; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011493:Protein Kinase C