Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials.
Previously, it has been reported that opioid peptides decrease the calcium component of action potentials in a dose-dependent and naloxone-reversible manner consistent with mediation by opiate receptors. To clarify the relation of mu and delta opiate receptors to decreases of somatic calcium-dependent action potential duration, we investigated the potency of two opioid peptides which have different affinities for mu and delta opiate receptors, Leu-enkephalin and morphiceptin. We predicted that Leu-enkephalin would be about 1000-fold more potent than morphiceptin on dorsal root ganglion (DRG) neurons if delta receptors mediated decreases of DRG neuron somatic calcium-dependent action potentials, but that these ligands would be approximately equipotent if mu receptors mediated opiate actions. Additionally, because naloxone has been reported to have a higher affinity for mu receptors in comparison with delta receptors, we investigated agonist sensitivity to naloxone antagonism. When morphiceptin and Leu-enkephalin were tested at equimolar concentrations on individual DRG neurons, a heterogeneous pattern of response to the two opioid peptides was obtained. The response pattern ranged from Leu-enkephalin and morphiceptin producing equal effects to Leu-enkephalin, but not morphiceptin, decreasing action potential duration. DRG neurons that responded only to Leu-enkephalin were approximately 100-fold less sensitive to naloxone antagonism than DRG neurons that responded equally well to both opioid peptides. DRG neurons that responded to both opioid peptides but better to Leu-enkephalin were intermediate in sensitivity to naloxone antagonism. Our results suggest that both mu and delta opiate receptors mediate decreases in somatic calcium-dependent action potentials of DRG neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D066298:In Vitro Techniques; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013997:Time Factors
D004723:Endorphins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; C028889:morphiceptin; D002118:Calcium