Elsevier

Brain Research

Volume 696, Issues 1–2, 23 October 1995, Pages 97-105
Brain Research

Dual regulation by μ, δ and κ opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma × DRG neuron hybrid F11 cells

https://doi.org/10.1016/0006-8993(95)00789-SGet rights and content

Abstract

The effects of the μ opioid receptor agonists, morphine and Tyr-d-Ala-Gly-N-methyl-Phe-Gly-ol (DAGO), the δ opioid receptor agonist, Tyr-d-Pen-Gly-Phe-d-penicillamine (DPDPE0 and the κ-opiod receptor agonist, dynorphin A-(1–13) on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and neuroblastoma × DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in IK (within 1 min), followed by a sustained decrease in IK. In contrast, μM concentrations rapidly elicited a sustained increase in IK. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in IK evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in IK. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual μM opioid-induced increases IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to μM as well as nM opioids. The results suggest that μ, δ and κ 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 IK 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.

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