title: Endomorphin-2 axon terminals contact mu-opioid receptor-containing dendrites in trigeminal dorsal horn.
abstract: The endomorphins represent a novel group of endogenous opioid peptides that have high affinity for the mu-opioid receptor (MOR1). Endomorphin-2 is present in high density in the spinal and trigeminal dorsal horns and is localized to primary afferents. If endomorphin-2 were an endogenous ligand for the MOR1, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemical methods combined with electron microscopy to determine if a cellular substrate exists for functional interactions between endomorphin-2 and MOR1. We confirmed the localization of endomorphin-2 to unmyelinated axons and axon terminals in the trigeminal dorsal horn. A small proportion of these endomorphin-2 axons contained MOR1, but many of the dendritic targets of endomorphin-2 terminals contained MOR1. Consistent with previous studies, endomorphin-2 was contained primarily in dense core vesicles and MOR1 was located primarily at non-synaptic sites. These morphological characteristics are consistent with the hypothesis that peptides are released extra-synaptically and their receptors may be located at sites distal to the synaptic junction. These anatomical data support the hypothesis that endomorphin-2 is a ligand for MORs in the trigeminal dorsal horn, particularly at postsynaptic sites.
authors.affiliation: Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. aichers@ohsu.edu
authors.forename: Sue A
authors.initials: SA
authors.lastname: Aicher
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitchell
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Swanson
authors.forename: James E
authors.initials: JE
authors.lastname: Zadina
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000166:cytology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology*
chemical_list: D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2