OPIOID-PEPTIDES WITH DIFFERENTIAL AFFINITY FOR MU-RECEPTOR AND DELTA-RECEPTOR DECREASE SENSORY NEURON CALCIUM-DEPENDENT ACTION-POTENTIALS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (2) , 394-402
Abstract
Opioid peptides were reported to decrease the Ca 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 Ca-dependent action potential duration, the potency of 2 opioid peptides which have different affinities for .mu. and .delta. opiate receptors, Leu-enkephalin and morphiceptins, were investigated in mice. The hypothesis that Leu-enkephalin would be .apprx. 1000-fold more potent than morphiceptin on dorsal root ganglion (DRG) neurons if .delta. receptors mediated decreases of DRG neuron somatic Ca-dependent action potentials, but these ligands would be approximately equipotent if .mu. receptors mediated opiate actions were tested. Because naloxone was reported to have a higher affinity for .mu. receptors in comparison with .delta. receptors agonist sensitivity to naloxone antagonism was also investigated. When morphiceptin and Leu-enkephalin were tested at equimolar concentrations on individual DRG neurons, a heterogeneous pattern of response to the 2 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 .apprx. 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. Evidently, both .mu. and .delta. opiate receptors mediate decreases in somatic Ca-dependent action potentials of DRG neurons. A variable receptor distribution may exist such that a proportion of DRG neurons have either predominantly .mu. or .delta. receptors, while some DRG neurons have both receptor types on their somatic membranes.

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