DUAL REGULATION BY MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID RECEPTOR AGONISTS OF K+ CONDUCTANCE OF DRG NEURONS AND NEUROBLASTOMA X DRG NEURON HYBRID F11 CELLS

The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gl-N-methyl-Phe-Gl-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D-penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13) on the whole-cell K+ currents (I-K) of cultured mouse DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in I-K (within 1 min), followed by a sustained decrease in I-K. In contrast, mu M concentrations rapidly elicited a sustained increase in I-K. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in I-K evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in I-K. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual mu M opioid-induced increases in I-K no longer occurred and more than half of the cells responded with a sustained decrease of I-K to mu M as well as nM opioids. The results suggest that mu, delta and kappa opioid receptors are each coupled to K+ channels through CTX-B- and PTX-sensitive transduction systems. Both systems have similar threshold concentrations to opioids. Activation of the CTX-B-sensitive opioid receptor/transduction system resulted in a decrease in K+ conductance of the cell which is generally associated with an increase in neuronal excitability. Activation of the other system resulted in an increase in K+ conductance which will, in general, decrease neuronal excitability. The net change in the I-K depends upon which effect predominates. The dominance at different opioid concentrations may depend on the relative efficacies of the coupling of these two systems to K+ channels.