INHIBITORY ACTIONS OF DELTA(1)-OPIOID, DELTA(2)-OPIOID, AND MU-OPIOIDRECEPTOR AGONISTS ON EXCITATORY TRANSMISSION IN LAMINA-II NEURONS OF ADULT-RAT SPINAL-CORD

This study examined the electrophysiological consequences of selective activation of delta(1)-, delta(2)-, or mu-opioid receptors using whol e-cell recordings made from visually identified lamina II neurons in t hin transverse slices of young adult rat lumbar spinal cord. Excitator y postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked elec trically at the ipsilateral dorsal root entry zone after blocking inhi bitory inputs with bicuculline and strychnine, and NMDA receptors with D-2-amino-5-phosphonopentanoic acid. Bath application of the mu recep tor agonist [D-Ala(2), N-MePhe(4), Gly(5)-ol]enkephalin (DAMGO) or the delta(1) receptor agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) prod uced a log-linear, concentration-dependent reduction in the amplitude of the evoked EPSP/ EPSC. By comparison, the delta(2) receptor agonist [D-Ala(2), Glu(4)]deltorphin (DELT) was unable to reduce the evoked E PSP/EPSC by more than 50% at 100 mu M, the highest concentration teste d. At concentrations that reduced evoked EPSP/EPSCs by 40-60%, neither DAMGO, DPDPE, nor DELT decreased the amplitude of the postsynaptic cu rrent produced by brief pressure ejection of pha-amino-3-hydroxy-5-met hyl-4-isoxazole-propionic acid, suggesting a presynaptic site of actio n of these opioid receptor agonists. Bath application of 200 nM naltri ben (NTB), a delta(2) receptor antagonist, competitively increased the EC(75) of DELT by 15.3-fold, but did not antagonize either DPDPE or D AMGO. The EC(75) of DELT was further increased by 169.7-fold in the pr esence of 1 mu M NTB. However, this high concentration of NTB also inc reased the EC(50) of DPDPE by about threefold in a noncompetitive mann er and antagonized DAMGO in a noncompetitive manner. In contrast, bath application of 33 or 100 nM 7-benzylidenenaltrexone (BNTX), a delta(1 ) receptor antagonist, produced a concentration-dependent, noncompetit ive antagonism of DPDPE, but did not antagonize DELT. A modest noncomp etitive antagonism of DAMGO occurred in the presence of 100 nM BNTX. B ath application of 500 nM naloxone competitively antagonized DAMGO as well as DPDPE, increasing their EC(50) values by 13.3- and 2.5-fold, r espectively. These results provide the first electrophysiological demo nstration of functional subtypes of the delta-opioid receptor in rat s pinal cord and indicate that activation of either delta(1)- or delta(2 )-opioid receptors inhibits excitatory, glutamatergic afferent transmi ssion in the spinal cord. This effect may mediate the ability of delta (1) or delta(2) receptor agonists to produce antinociception when admi nistered intrathecally in the rat.