Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells.

Abstract

The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N-methyl-Phe-Gly-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 (IK) 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 IK (within 1 min), followed by a sustained decrease in IK. In contrast, microM 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 microM opioid-induced increases in IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to microM 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 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.

• Authors: S F Fan, S M Crain
• Journal: Brain research (Brain Res) Vol. 696 Issue 1-2 Pg. 97-105 (Oct 23 1995) ISSN: 0006-8993 [Print] Netherlands
• PMID: 8574691 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Potassium Channels
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Virulence Factors, Bordetella
• Cholera Toxin
• Pertussis Toxin

Topics

• Amino Acid Sequence
• Animals
• Brain Neoplasms (metabolism)
• Cholera Toxin (pharmacology)
• Ganglia, Spinal (cytology, drug effects, metabolism)
• Hybrid Cells
• Mice
• Molecular Sequence Data
• Neuroblastoma (metabolism)
• Neurons (drug effects, metabolism)
• Patch-Clamp Techniques
• Pertussis Toxin
• Potassium Channels (drug effects, metabolism)
• Receptors, Opioid (agonists)
• Receptors, Opioid, delta (agonists)
• Receptors, Opioid, kappa (agonists)
• Receptors, Opioid, mu (agonists)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured
• Virulence Factors, Bordetella (pharmacology)