Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles

Zhang, X; Liu, Bao; Arvidsson, Ulf; Elde, Robert; Hökfelt, Tomas

doi:10.1016/s0306-4522(97)00341-2

Cited by 148 publications

(152 citation statements)

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“…Double immunofluorescence staining showed that DORs were present in SP-and CGRP-positive LDCVs in small DRG neurons in mice ( Figure 2A and Supplementary information, Figure S2A). This immunostaining pattern, which was shown with antibodies against DOR1 [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] , was abolished by the deletion of Oprd1 exon 1 in mice (Supplementary information, Figure S2A). Furthermore, β2 AR, G αi2 , PLCβ2, VGCC α2δ1 and P2X purinoceptor 2 (P2X 2 ) were present in SP-positive LDCVs in small DRG neurons (Figure 2A).…”

Section: Ldcv Localization Of Gpcrs Signaling Molecules and Ion Chanmentioning

confidence: 78%

“…We noticed that DOR1 [9,12] and serotonin receptor 1D (5-HT-1D) [22], which have been detected in LDCVs in small DRG neurons, were not detected by the LC-MS method because of low expression levels. To compensate for this methodological disadvantage, we carried out immunoblot analysis of 13 GPCRs, which are expressed in DRG neurons [23], in the subcellular fractions.…”

Section: Analysis Of the Protein Composition Of Ldcvsmentioning

confidence: 98%

“…Chromogranin B (CGB) [16,17] and DOR1 [9,12] were used as markers for the LDCV fractions ( Figure 1A). The specificity of the antibodies against DOR1 was confirmed by the absence of immunoblot signal in the spinal cord of Oprd1 exon 1-deleted mice (Supplementary information, Figure S1A).…”

Section: Analysis Of the Protein Composition Of Ldcvsmentioning

confidence: 99%

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Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

Zhao

Wang

et al. 2011

Cell Res

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Stimulus-induced exocytosis of large dense-core vesicles (LDCVs) leads to discharge of neuropeptides and fusion of LDCV membranes with the plasma membrane. However, the contribution of LDCVs to the properties of the neuronal membrane remains largely unclear. The present study found that LDCVs were associated with multiple receptors, channels and signaling molecules, suggesting that neuronal sensitivity is modulated by an LDCV-mediated mechanism. Liquid chromatography-mass spectrometry combined with immunoblotting of subcellular fractions identified 298 proteins in LDCV membranes purified from the dorsal spinal cord, including G-protein-coupled receptors, G-proteins and other signaling molecules, ion channels and trafficking-related proteins. Morphological assays showed that δ-opioid receptor 1 (DOR1), β2 adrenergic receptor (AR), G αi2 , voltage-gated calcium channel α2δ1 subunit and P2X purinoceptor 2 were localized in substance P (SP)-positive LDCVs in small-diameter dorsal root ganglion neurons, whereas β1 AR, Wnt receptor frizzled 8 and dishevelled 1 were present in SP-negative LDCVs. Furthermore, DOR1/G αi2 /G β1γ5 /phospholipase C β2 complexes were associated with LDCVs. Blockade of the DOR1/ G αi2 interaction largely abolished the LDCV localization of G αi2 and impaired stimulation-induced surface expression of G αi2 . Thus, LDCVs serve as carriers of receptors, ion channels and preassembled receptor signaling complexes, enabling a rapid, activity-dependent modulation of neuronal sensitivity.

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Section: Ldcv Localization Of Gpcrs Signaling Molecules and Ion Chanmentioning

confidence: 78%

Section: Analysis Of the Protein Composition Of Ldcvsmentioning

confidence: 98%

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Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

Zhao

Wang

et al. 2011

Cell Res

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“…By contrast, drugs acting on ␦OR produce more limited analgesia, but also give rise to considerably less undesirable side-effects and induce virtually no tolerance (Porreca et al, 1984;May et al, 1989; Sheldon et al, 1990;Szeto et al, 1999;Gallantine and Meert, 2005). For these reasons, ␦OR agonists have been proposed as possible alternatives to OR agonists for the treatment of chronic pain, including neuropathic (Mika et al, 2001;Petrillo et al, 2003;Morinville et al, 2004a) and chronic inflammatory pain (Desmeules et al, 1993;Stewart and Hammond, 1994;Fraser et al, 2000;Hurley and Hammond, 2000;Qiu et al, 2000;Cahill et al, 2003;Petrillo et al, 2003).One of the reasons for the relatively poor analgesic efficiency of ␦OR agonists may be that only a small proportion of ␦OR is actually present on neuronal plasma membranes under baseline conditions (Cheng et al, 1995(Cheng et al, , 1997Elde et al, 1995;Zhang et al, 1998;Cahill et al, 2001a). However, under conditions of chronic inflammation, such as produced in rodents by injection of complete Freund's adjuvant (CFA) in the hind paw, we observed a massive recruitment of ␦OR from intracellular stores to the plasma membrane in neurons of the dorsal horn of the spinal cord Morinville et al, 2004b).…”

mentioning

confidence: 99%

“…One of the reasons for the relatively poor analgesic efficiency of ␦OR agonists may be that only a small proportion of ␦OR is actually present on neuronal plasma membranes under baseline conditions (Cheng et al, 1995(Cheng et al, , 1997Elde et al, 1995;Zhang et al, 1998;Cahill et al, 2001a). However, under conditions of chronic inflammation, such as produced in rodents by injection of complete Freund's adjuvant (CFA) in the hind paw, we observed a massive recruitment of ␦OR from intracellular stores to the plasma membrane in neurons of the dorsal horn of the spinal cord Morinville et al, 2004b).…”

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confidence: 99%

Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin

et al. 2007

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Abstract-We previously showed that prolonged morphine treatment and chronic inflammation both enhanced delta opioid receptor (␦OR) cell surface density in lumbar spinal cord neurons. Here, we sought to determine whether administration of morphine to rats with chronic inflammation would further increase the bio-availability of ␦OR, and thereby the analgesic properties of the ␦OR agonist deltorphin, over that produced by inflammation alone. We found that chronic inflammation produced by injection of complete Agonists acting through the mu opioid receptor ( OR), such as morphine and its derivatives, induce potent analgesic effects (Bodnar and Klein, 2004). However, they also give rise to undesirable side-effects such as nausea, constipation, and respiratory depression (Colpaert, 1996;Kreek, 1996). In addition, chronic stimulation of OR induces tolerance and physical dependence (Cowan et al., 1988). By contrast, drugs acting on ␦OR produce more limited analgesia, but also give rise to considerably less undesirable side-effects and induce virtually no tolerance (Porreca et al., 1984;May et al., 1989; Sheldon et al., 1990;Szeto et al., 1999;Gallantine and Meert, 2005). For these reasons, ␦OR agonists have been proposed as possible alternatives to OR agonists for the treatment of chronic pain, including neuropathic (Mika et al., 2001;Petrillo et al., 2003;Morinville et al., 2004a) and chronic inflammatory pain (Desmeules et al., 1993;Stewart and Hammond, 1994;Fraser et al., 2000;Hurley and Hammond, 2000;Qiu et al., 2000;Cahill et al., 2003;Petrillo et al., 2003).One of the reasons for the relatively poor analgesic efficiency of ␦OR agonists may be that only a small proportion of ␦OR is actually present on neuronal plasma membranes under baseline conditions (Cheng et al., 1995(Cheng et al., , 1997Elde et al., 1995;Zhang et al., 1998;Cahill et al., 2001a). However, under conditions of chronic inflammation, such as produced in rodents by injection of complete Freund's adjuvant (CFA) in the hind paw, we observed a massive recruitment of ␦OR from intracellular stores to the plasma membrane in neurons of the dorsal horn of the spinal cord Morinville et al., 2004b). This increase in the pharmacological availability of ␦OR was postulated to account for the enhanced antihyperalgesic efficacy of the centrally administered ␦OR agonists reported in conditions of chronic inflammation (Hylden et al., 1991;Stewart and Hammond, 1994;Fraser et al., 1 Present address: Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4. *Corresponding author. Tel: ϩ1-514-398-1913; fax: ϩ1-514-398-5871. E-mail address: alain.beaudet@mcgill.ca (A. Beaudet). Abbreviations: CFA, complete Freund's adjuvant; DRG, dorsal root ganglion; Fluo-DLT, -Bodipy 576/589 deltorphin-I 5-aminopentylamide; i.t., intrathecal/intrathecally; MPAHE, maximum possible antihyperalgesic effect; MPE, maximum possible antinociceptive effect; MS, morphine sulfate; OR, mu opioid receptor; PB, phosphate buffer; RI...

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?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

Wang

Wessendorf

1999

J. Comp. Neurol.

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The rostral ventromedial medulla (RVM) is an important mediator of the supraspinal component of opioid antinociception. Previous studies have suggested that activation of the cloned μ‐ and δ‐opioid receptors (MOR1 and DOR1 respectively) in the RVM produces the antinociception mediated by spinally projecting neurons. In the present study, we investigated the expression of mRNA encoding either MOR1 or DOR1 in the RVM of rats. In addition, we examined quantitatively the expression of MOR1 and DOR1 mRNAs in spinally projecting RVM neurons including serotonergic (5HT) cells by using in situ hybridization, immunocytochemistry, retrograde tract‐tracing, and the physical disector. Brainstem neurons were labeled in 14 male Sprague‐Dawley rats by applying Fluoro‐Gold (FG) topically to the dorsal surface of the lumbosacral spinal cord. Five‐micrometer‐thick cryostat sections were cut and in situ hybridization was performed by using full‐length cRNA probes labeled with 35S‐UTP. We found that 43% of RVM projection neurons expressed MOR1 mRNA and 83% of RVM projection neurons expressed DOR1 mRNA. Of 192 retrogradely labeled cells in the RVM, 51 cells (27%) were immunoreactive for 5HT. Of this population, half appeared to be labeled for the mRNA encoding MOR1 and over three‐fourths appeared to be labeled for the mRNA encoding DOR1. Thus, we conclude that bulbospinal neurons express MOR1 and DOR1; moreover, MOR1 and DOR1 are expressed by significant proportions of 5HT neurons projecting to or through the dorsal spinal cord. J. Comp. Neurol. 404:183–196, 1999. © 1999 Wiley‐Liss, Inc.

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Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles

Cited by 148 publications

References 122 publications

Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin

?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

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