Mu-opioid receptor is present in dendritic targets of Endomorphin-2 axon terminals in the nuclei of the solitary tract

M. B. Silverman, S. M. Hermes, J. E. Zadina, Sue Aicher

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Endomorphins represent a group of endogenous opioid peptides with high affinity for the mu-opioid receptor. In the brainstem, Endomorphin-2 is found in trigeminal dorsal horn and the nuclei of the solitary tract, suggesting its presence in both nociceptive and visceral primary afferents. If Endomorphin-2 were an endogenous ligand for the mu-opioid receptor, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemistry combined with electron microscopy to examine interactions between Endomorphin-2-immunoreactive and mu-opioid receptor-immunoreactive profiles within the nuclei of the solitary tract in the rat. Endomorphin-2-immunoreactivity was found primarily in unmyelinated axons and axon terminals in nuclei of the solitary tract and the majority of these terminals contained dense core vesicles. Endomorphin-2-immunoreactive axon terminals often formed asymmetric synapses with dendritic spines lacking mu-opioid receptor-immunoreactivity, but mu-opioid receptor-immunoreactivity was found in many of the larger dendritic targets of Endomorphin-2-immunoreactive terminals. Thus, mu-opioid receptor-immunoreactivity was found in the postsynaptic targets of Endomorphin-2-immunoreactive axon terminals, consistent with the hypothesis that Endomorphin-2 is an endogenous ligand for this receptor within the nuclei of the solitary tract. A small number of Endomorphin-2- immunoreactive somata, dendrites, and axon terminals also contained mu-opioid receptor-immunoreactivity. Cells that contain both the opioid peptide and its receptor may be a substrate for potential autoregulation of nuclei of the solitary tract neurons by opioid ligands. Finally, using tract tracing and confocal microscopy, we found Endomorphin-2-immunoreactivity in a subset of vagal afferents. Together these findings support the hypothesis that Endomorphin-2 is a ligand for the mu-opioid receptor within nuclei of the solitary tract and that the peptide is at least partially derived from primary visceral afferents.

Original languageEnglish (US)
Pages (from-to)887-896
Number of pages10
JournalNeuroscience
Volume135
Issue number3
DOIs
StatePublished - 2005

Fingerprint

Solitary Nucleus
mu Opioid Receptor
Presynaptic Terminals
Visceral Afferents
Ligands
Opioid Peptides
endomorphin 2
Dendritic Spines
Peptides
Peptide Receptors
Secretory Vesicles
Carisoprodol
Dendrites
Confocal Microscopy
Synapses
Opioid Analgesics
Brain Stem
Axons
Electron Microscopy
Homeostasis

Keywords

  • Confocal microscopy
  • Electron microscopy
  • Endogenous opioid
  • Extrasynaptic receptors
  • Pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mu-opioid receptor is present in dendritic targets of Endomorphin-2 axon terminals in the nuclei of the solitary tract. / Silverman, M. B.; Hermes, S. M.; Zadina, J. E.; Aicher, Sue.

In: Neuroscience, Vol. 135, No. 3, 2005, p. 887-896.

Research output: Contribution to journalArticle

Silverman, M. B. ; Hermes, S. M. ; Zadina, J. E. ; Aicher, Sue. / Mu-opioid receptor is present in dendritic targets of Endomorphin-2 axon terminals in the nuclei of the solitary tract. In: Neuroscience. 2005 ; Vol. 135, No. 3. pp. 887-896.
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AU - Aicher, Sue

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AB - Endomorphins represent a group of endogenous opioid peptides with high affinity for the mu-opioid receptor. In the brainstem, Endomorphin-2 is found in trigeminal dorsal horn and the nuclei of the solitary tract, suggesting its presence in both nociceptive and visceral primary afferents. If Endomorphin-2 were an endogenous ligand for the mu-opioid receptor, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemistry combined with electron microscopy to examine interactions between Endomorphin-2-immunoreactive and mu-opioid receptor-immunoreactive profiles within the nuclei of the solitary tract in the rat. Endomorphin-2-immunoreactivity was found primarily in unmyelinated axons and axon terminals in nuclei of the solitary tract and the majority of these terminals contained dense core vesicles. Endomorphin-2-immunoreactive axon terminals often formed asymmetric synapses with dendritic spines lacking mu-opioid receptor-immunoreactivity, but mu-opioid receptor-immunoreactivity was found in many of the larger dendritic targets of Endomorphin-2-immunoreactive terminals. Thus, mu-opioid receptor-immunoreactivity was found in the postsynaptic targets of Endomorphin-2-immunoreactive axon terminals, consistent with the hypothesis that Endomorphin-2 is an endogenous ligand for this receptor within the nuclei of the solitary tract. A small number of Endomorphin-2- immunoreactive somata, dendrites, and axon terminals also contained mu-opioid receptor-immunoreactivity. Cells that contain both the opioid peptide and its receptor may be a substrate for potential autoregulation of nuclei of the solitary tract neurons by opioid ligands. Finally, using tract tracing and confocal microscopy, we found Endomorphin-2-immunoreactivity in a subset of vagal afferents. Together these findings support the hypothesis that Endomorphin-2 is a ligand for the mu-opioid receptor within nuclei of the solitary tract and that the peptide is at least partially derived from primary visceral afferents.

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KW - Extrasynaptic receptors

KW - Pain

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