Preferential Cytoplasmic Localization of δ-Opioid Receptors in Rat Striatal Patches: Comparison with Plasmalemmal μ-Opioid Receptors

Abstract

The activation of ␦-opioid receptors (DORs) in the caudateputamen nucleus (CPN) produces regionally distinct changes in motor functions, many of which are also influenced by opioids active at -opioid receptors (MORs). These actions most likely occur in MOR-enriched patch compartments in the CPN. To determine the functional sites for DOR activation and potential interactions involving MOR in these regions, immunoperoxidase and immunogold-silver labeling methods were applied reversibly for the ultrastructural localization of DOR and MOR in single rat brain sections containing patches of the CPN. DOR immunoreactivity was commonly seen within the cytoplasm of spiny and aspiny neurons, many of which also expressed MOR. In dendrites and spines, DOR labeling was preferentially localized to membranes of the smooth endoplasmic reticulum and spine apparatus, whereas MOR showed a prominent plasmalemmal distribution. DOR-and/or MOR-labeled spines received asymmetric, excitatory synapses, some of which showed notable perforations, suggesting the involvement of these receptors in activity-dependent synaptic plasticity. DORs were more frequently detected than were MORs within axon terminals that formed either asymmetric synapses with spine heads or symmetric synapses with spine necks. Our results suggest that in striatal patches, DORs, often in cooperation with MORs, play a direct modulatory role in controlling the postsynaptic excitability of spines, whereas presynaptic neurotransmitter release onto spines is mainly influenced by DOR activation. In comparison with MOR, the prevalent association of DOR with cytoplasmic organelles that are involved in intracellular trafficking of cell surface proteins suggests major differences in availability of these receptors to extracellular opioids.

Knockin mice expressing fluorescent δ-opioid receptors uncover G protein-coupled receptor dynamics in vivo

“…5C). This fluorescence likely represents a receptor reserve, concordant with previous indications of intracellular DOR pools (21,32,33). In SNC80-treated animals, cell bodies with the typical intense punctate fluorescence were obvious throughout the nervous system (Fig.…”

Translocation of Dynorphin Neuropeptides across the Plasma Membrane

“…A large proportion of ␦-opioid receptors are located in the neuronal cytoplasm where they are associated with the endoplasmic reticulum and Golgi apparatus (89,90). In dendrites and dendritic spines, ␦-opioid receptors are preferentially localized to membranes of the smooth endoplasmic reticulum and spine apparatus.…”

Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain

“…Some of these changes affect the expression and subcellular distribution of dOR in neurons of the dorsal horn of the spinal cord and dorsal root ganglia (Besse et al, 1992;Cahill et al, 2003;Ji et al, 1995). Under basal conditions, dOR are almost exclusively localized to intracellular compartments in neurons throughout the CNS, including the spinal cord (Arvidsson et al, 1995;Cahill et al, 2001a,b;Cheng et al, 1995;Morinville et al, 2003;Svingos et al, 1995;Wang and Pickel, 2001;Zhang et al, 1998). Hence, ultra-structural analysis revealed that in the rat spinal cord, plasma membrane-associated dOR accounted for less than 10% of the total amount of immunoreactive dOR detected within dendrites of dorsal horn neurons (Cahill et al, 2001a,b;Morinville et al, 2003).…”