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Journal of Neuroscience, Vol 14, 4965-4971, Copyright © 1994 by Society for Neuroscience
Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord
SR Glaum, RJ Miller and DL Hammond
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
This study examined the electrophysiological consequences of selective
activation of delta 1-, delta 2-, or mu-opioid receptors using whole- cell
recordings made from visually identified lamina II neurons in thin
transverse slices of young adult rat lumbar spinal cord. Excitatory
postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked
electrically at the ipsilateral dorsal root entry zone after blocking
inhibitory inputs with bicuculline and strychnine, and NMDA receptors with
D-2-amino-5-phosphonopentanoic acid. Bath application of the mu receptor
agonist [D-Ala2, N-MePhe4, Gly5-ol]enkephalin (DAMGO) or the delta 1
receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) produced a long-linear,
concentration-dependent reduction in the amplitude of the evoked EPSP/EPSC.
By comparison, the delta 2 receptor agonist [D- Ala2,Glu4]deltorphin (DELT)
was unable to reduce the evoked EPSP/EPSC by more than 50% at 100 microM,
the highest concentration tested. At concentrations that reduced evoked
EPSP/EPSCs by 40-60%, neither DAMGO, DPDPE, nor DELT decreased the
amplitude of the postsynaptic current produced by brief pressure ejection
of (S)-alpha-amino-3-hydroxy-5- methyl-4-isoxazole-propionic acid,
suggesting a presynaptic site of action of these opioid receptor agonists.
Bath application of 200 nM naltriben (NTB), a delta 2 receptor antagonist,
competitively increased the EC75 of DELT by 15.3-fold, but did not
antagonize either DPDPE or DAMGO. The EC75 of DELT was further increased by
169.7-fold in the presence of 1 microM NTB. However, this high
concentration of NTB also increased the EC50 of DPDPE by about threefold in
a noncompetitive manner and antagonized DAMGO in a noncompetitive
manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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