title: Mu-opioid receptor is present in dendritic targets of Endomorphin-2 axon terminals in the nuclei of the solitary tract.
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.
authors.affiliation: Oregon Health & Science University, Neurological Sciences Institute, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Silverman
authors.forename: S M
authors.initials: SM
authors.lastname: Hermes
authors.forename: J E
authors.initials: JE
authors.lastname: Zadina
authors.forename: S A
authors.initials: SA
authors.lastname: Aicher
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000378:metabolism; D009842:Oligopeptides / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D017552:Solitary Nucleus / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D009842:Oligopeptides; C485765:Oprm1 protein, rat; D017450:Receptors, Opioid, mu; C105294:endomorphin 2