Activation of mu-opioid receptor selectively potentiates NMDA-induced outward currents in rat locus coeruleus neurons.
We investigated the opioid modulation of N-methyl-d-aspartic acid (NMDA) receptor-mediated response in dissociated LC neurons using nystatin-perforated patch recording. In Mg(2+)-free extracellular solution, NMDA induced an inward current (I(NMDA-IN)) and a subsequent outward current (I(NMDA-OUT)) at a holding potential of -40 mV. A selective mu-opioid receptor agonist, d-Ala(2),N-MePhe(4),Gly(5)-ol-enkephalin (DAMGO), potentiated I(NMDA-OUT) in a concentration-dependent manner with the half-maximal effective concentration of 0.7 microM, while DAMGO (0.1-10 microM) did not affect I(NMDA-IN). Under the condition of I(NMDA-OUT) blockade by the use of Cs-based pipette solution or by buffering intracellular Ca(2+) with a high concentration of EGTA and zero Ca(2+), DAMGO did not change I(NMDA-IN). The DAMGO potentiation of I(NMDA-OUT) was prevented by naloxone, an opioid receptor antagonist. In addition, the DAMGO potentiation of I(NMDA-OUT) was prevented by treatment with staurosporine, a broad spectrum protein kinase inhibitor. In conclusion, mu-opioid receptor activation selectively potentiated I(NMDA-OUT) via intracellular signal pathway without affecting I(NMDA-IN) in LC neurons. We suggest the inhibitory opioid effect through NMDA receptor-mediated response in LC neurons.
Koyama
Susumu
S
Cellular and Systems Physiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan. susumuk@fukuoka-u.ac.jp
Akaike
Norio
N
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D016202:N-Methylaspartate