Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium-dependent action potential duration.
Opioid peptides decrease somatic calcium-dependent action potential duration of a subpopulation of mouse dorsal root ganglion (DRG) neurons grown in dissociated cell culture. Based on rank order of potency and naloxone sensitivity, both mu and delta opioid receptors were demonstrated on the somata of DRG neurons and were shown to have a heterogeneous distribution. The purpose of the present investigation was to determine the actions of dynorphin gene products, dynorphin A, dynorphin B, dynorphin A(1-8), dynorphin A(1-9), alpha-neoendorphin and beta-neoendorphin on DRG neuron somatic calcium-dependent action potentials and to compare the actions of dynorphin and neoendorphin peptides to the action of morphiceptin, a mu receptor-selective ligand, and Leu-enkephalin, a delta receptor-preferring ligand. We report that the dynorphin and neoendorphin peptides decreased DRG neuron somatic calcium-dependent action potential duration in a portion of DRG neurons, an action that was dose-dependent and was antagonized by naloxone. DRG neuron responses to the dynorphins and neoendorphins differed from responses to morphiceptin and Leu-enkephalin. First, many DRG neurons responded to dynorphin A but not to morphiceptin or Leu-enkephalin. Second, dynorphin A responses, unlike responses to morphiceptin or Leu-enkephalin, were present after intracellular injection of cesium, a potassium channel blocker. Dynorphin A effectiveness was decreased after deletions at the carboxy-terminus and Leu-enkephalin [dynorphin A(1-5)] was inactive at 10 microM. Thus, on DRG neurons in cell culture, dynorphins and neoendorphins act at opioid receptors distinct from mu and delta receptors, possibly kappa receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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Werz
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Macdonald
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors; D001615:beta-Endorphin / Q000031:analogs & derivatives*
D004723:Endorphins; D007473:Ion Channels; D011498:Protein Precursors; D011957:Receptors, Opioid; C030738:dynorphin receptor; D009270:Naloxone; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; C025681:alpha-neoendorphin; D004399:Dynorphins; C030719:beta-neo-endorphin; C028889:morphiceptin; D012964:Sodium; D002118:Calcium