Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials

Abstract

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)