Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion

Neuron. 2003 Jan 9;37(1):121-33. doi: 10.1016/s0896-6273(02)01103-0.

Abstract

Here we describe a novel mechanism for plasma membrane insertion of the delta opioid receptor (DOR). In small dorsal root ganglion neurons, only low levels of DORs are present on the cell surface, in contrast to high levels of intracellular DORs mainly associated with vesicles containing calcitonin gene-related peptide (CGRP). Activation of surface DORs caused Ca(2+) release from IP(3)-sensitive stores and Ca(2+) entry, resulting in a slow and long-lasting exocytosis, DOR insertion, and CGRP release. In contrast, membrane depolarization or activation of vanilloid and P2Y(1) receptors induced a rapid DOR insertion. Thus, DOR activation induces a Ca(2+)-dependent insertion of DORs that is coupled to a release of excitatory neuropeptides, suggesting that treatment of inflammatory pain should include blockade of DORs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Fluorescent Antibody Technique
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / ultrastructure
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / ultrastructure
  • Neuropeptides / metabolism
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Nociceptors / ultrastructure
  • PC12 Cells
  • Pain / metabolism
  • Pain / physiopathology
  • Rats
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2Y1
  • Secretory Vesicles / metabolism
  • Secretory Vesicles / ultrastructure

Substances

  • Neuropeptides
  • P2ry1 protein, mouse
  • Receptors, Drug
  • Receptors, Neurotransmitter
  • Receptors, Opioid, delta
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y1
  • Calcitonin Gene-Related Peptide
  • Calcium