Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia

Mennicken, Françoise; Zhang, Ji; Hoffert, Cyrla; Ahmad, Sultan; Beaudet, Alain; O’Donnell, Dajan

doi:10.1002/cne.10839

Cited by 73 publications

(102 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%

“…After three PBS washes, cells were labeled with the primary antibodies. We used antibodies against DOR1 [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] (1:30 000; DiaSorin), G αi2 (1:100; Santa Cruz), G β1 (1:200; Santa Cruz), G γ5 (1:400; Santa Cruz), PLCβ2 (1:200; Santa Cruz), P2X 2 (1:1 000; Chemicon), Fzd8 (1:400; Everest Biotech), β1 AR (1:400; Santa Cruz), β2 AR (1:200; Santa Cruz), SP (1:500; Neuromics), CGRP (1:500; Biogenesis), Dvl1 (1:200; a gift from Dr. Zhen-Ge Luo), VGCC α2δ1 (1:100; Affinity BioReagents) and Myc (1:500; a gift from Dr Jin-Qiu Zhou).…”

Section: Immunostainingmentioning

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: Immunostainingmentioning

confidence: 99%

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

Zhao

Wang

et al. 2011

Cell Res

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“…Therefore, the antiserum primarily recognizes DOR1, although an excessive amount of antiserum might generate nonspecific binding. Using the antibodies above at a dilution of 1:30,000, we found that DORs were present in peptidergic and vanilloid receptor type 1-ir small neurons ( Interestingly, we found the presence of DORs on the cell surface in ∼14% of DRG neurons when we tested another antibody, now against DOR1 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] (1:60,000-120,000; Alomone) that also recognized Myc-DOR1 expressed in HEK293 cells ( Fig. 3 H and I and Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DOR1 mRNA has been found in many DRG neurons, including large ones, and at lower levels in both isolectin B4-negative (IB4 − , peptidergic) and IB4-positive (IB4 + ) subsets of small neurons (10)(11)(12). In neurons of the painmodulating system, intracellular DORs are inserted into the plasma membrane following a variety of chemical and behavioral stimuli, including sustained pain conditions and chronic opioids (13)(14)(15)(16)(17).…”

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confidence: 99%

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Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons

Wang

Zhao²,

Zhong

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

192

204

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Morphine-induced analgesia and antinociceptive tolerance are known to be modulated by interaction between δ-opioid receptors (DORs) and μ-opioid receptors (MORs) in the pain pathway. However, evidence for expression of DORs in nociceptive small-diameter neurons in dorsal root ganglia (DRG) and for coexistence of DORs with MORs and neuropeptides has recently been challenged. We now report, using in situ hybridization, single-cell PCR, and immunostaining, that DORs are widely expressed not only in large DRG neurons but in small ones and coexist with MORs in peptidergic small DRG neurons, with protachykinin-dependent localization in large dense-core vesicles. Importantly, both DOR and MOR agonists reduce depolarization-induced Ca 2+ currents in single small DRG neurons and inhibit afferent C-fiber synaptic transmission in the dorsal spinal cord. Thus, coexistence of DORs and MORs in small DRG neurons is a basis for direct interaction of opioid receptors in modulation of nociceptive afferent transmission and opioid analgesia.

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Comparison between δ‐opioid receptor functional response and autoradiographic labeling in rat brain and spinal cord

Pradhan

Clarke

2004

J of Comparative Neurology

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The distribution of delta-opioid receptors (DORs) in the rat central nervous system has been previously characterized by radioligand binding and immunohistochemistry. However, the functional neuroanatomy of DORs has not been mapped in any detail; this is potentially important, because these receptors appear to be primarily cytosolic. Opioid receptors can couple to G(i/o) G proteins, a process that is detected by agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding. The purpose of this study was therefore to determine the distribution of functional DORs, as assessed by [35S]GTPgammaS autoradiographic labeling in response to the DOR agonist deltorphin II. For comparison, adjacent sections were labeled with [125I]deltorphin II or the DOR antagonist [125I]AR-M100613. In all three assays, mu-opioid receptors were blocked pharmacologically. The distributions of [125I]deltorphin II and [125I]AR-M100613 were highly correlated but not identical. Deltorphin II increased [35S]GTPgammaS binding in a concentration-dependent and naltrindole-sensitive manner. The regional [35S]GTPgammaS response to deltorphin II was only moderately predicted by agonist or antagonist radioligand binding (r = 0.67 and 0.50, respectively). [35S]GTPgammaS responses to deltorphin II were strongest in the extended striatum (caudate putamen, nucleus accumbens, olfactory tubercle) and cerebral cortex. In contrast, some areas reported to mediate DOR analgesia (brainstem, spinal cord) possessed a much lower [35S]GTPgammaS response. These findings demonstrate the existence of a partial mismatch between DOR radioligand binding and [35S]GTPgammaS response. This divergence possibly reflects regional heterogeneity in G-protein receptor coupling, or in the subcellular localization of DOR.

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Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia

Cited by 73 publications

References 50 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

Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons

Comparison between δ‐opioid receptor functional response and autoradiographic labeling in rat brain and spinal cord

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