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Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium-dependent action potential duration.

M A Werz, R L Macdonald

    The Journal of Pharmacology and Experimental Therapeutics
    |July 1, 1985
    PubMed
    Summary
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    Dynorphin and neoendorphin peptides reduce action potential duration in mouse dorsal root ganglion neurons. These effects suggest dynorphins and neoendorphins act on opioid receptors distinct from mu and delta types, possibly kappa receptors.

    Area of Science:

    • Neuroscience
    • Pharmacology
    • Molecular Biology

    Background:

    • Opioid peptides are known to modulate neuronal excitability.
    • Previous studies demonstrated mu and delta opioid receptors on dorsal root ganglion (DRG) neurons.
    • The specific actions of dynorphin and neoendorphin peptides on DRG neurons were not fully characterized.

    Purpose of the Study:

    • To investigate the effects of dynorphin and neoendorphin peptides on calcium-dependent action potentials in mouse DRG neurons.
    • To compare the receptor actions of dynorphin/neoendorphin peptides with known mu (morphiceptin) and delta (Leu-enkephalin) receptor ligands.

    Main Methods:

    • Cultured mouse dorsal root ganglion (DRG) neurons were used.
    • Electrophysiological recordings measured somatic calcium-dependent action potential duration.

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  • Dose-response relationships and naloxone sensitivity were assessed.
  • Effects were examined after intracellular cesium injection (potassium channel blocker).

    • Main Results:

    • Dynorphin and neoendorphin peptides decreased action potential duration in a subpopulation of DRG neurons.
    • These effects were dose-dependent and antagonized by naloxone.
    • DRG neuron responses to dynorphins/neoendorphins differed from morphiceptin and Leu-enkephalin, with some neurons responding to dynorphin A but not the others.
    • Dynorphin A's action persisted after cesium injection, unlike morphiceptin/Leu-enkephalin responses.
    • Truncated dynorphin A peptides showed reduced or no activity, indicating carboxy-terminal importance.

    Conclusions:

    • Dynorphins and neoendorphins act on opioid receptors in DRG neurons that are distinct from classical mu and delta receptors.
    • The data suggest the involvement of kappa opioid receptors.
    • These findings contribute to understanding the diverse roles of opioid peptides in sensory neuron function.