δ-opioid receptor
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Location (UCSC) | Chr 1: 28.81 – 28.87 Mb | Chr 4: 131.84 – 131.87 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The δ-opioid receptor, also known as delta
Function
The endogenous system of opioid receptors is well known for its analgesic potential; however, the exact role of δ-opioid receptor activation in pain modulation is largely up for debate. This also depends on the model at hand since receptor activity is known to change from species to species. Activation of delta receptors produces
Evidence for whether delta agonists produce
Of additional interest is the potential for delta agonists to be developed for use as a novel class of
Another interesting aspect of δ-opioid receptor function is the suggestion of μ/δ-opioid receptor interactions. At the extremes of this suggestion lies the possibility of a μ/δ opioid receptor oligomer. The evidence for this stems from the different binding profiles of typical mu and delta agonists such as morphine and DAMGO respectively, in cells that coexpress both receptors compared to those in cells that express them individually. In addition, work by Fan and coworkers shows the restoration of the binding profiles when distal carboxyl termini are truncated at either receptor, suggesting that the termini play a role in the oligomerization.
Recent work indicates that exogenous ligands that activate the delta receptors mimic the phenomenon known as ischemic preconditioning.[21] Experimentally, if short periods of transient ischemia are induced the downstream tissues are robustly protected if longer-duration interruption of the blood supply is then affected. Opiates and opioids with DOR activity mimic this effect. In the rat model, introduction of DOR ligands results in significant cardioprotection.[22]
Ligands
Until comparatively recently, there were few pharmacological tools for the study of δ receptors. As a consequence, our understanding of their function is much more limited than those of the other opioid receptors for which selective ligands have long been available.
However, there are now several selective δ-opioid receptor agonists available, including peptides such as DPDPE and deltorphin II, and non-peptide drugs such as SNC-80,[23] the more potent (+)-BW373U86,[24] a newer drug DPI-287, which does not produce the problems with convulsions seen with the earlier agents,[25] and the mixed μ/δ agonist DPI-3290, which is a much more potent analgesic than the more highly selective δ agonists.[26] Selective antagonists for the δ receptor are also available, with the best known being the opiate derivative naltrindole.[27]
Agonists
- Peptides
- Non-peptides
- ADL-5859[28]
- BU-48
- BW373U86
- DPI-221
- DPI-287
- DPI-3290
- RWJ-394674-
- SNC-80
- TAN-67
- Amoxapine (partial agonist)[29]
- Cannabidiol (allosteric modulator, non-selective)[30]
- Desmethylclozapine
- Mitragynine[31]
- Mitragynine pseudoindoxyl[31]
- Norbuprenorphine (peripherally restricted)
- N-Phenethyl-14-ethoxymetopon
- 7-Spiroindanyloxymorphone
- Tetrahydrocannabinol (allosteric modulator, non-selective)[30]
- Xorphanol
Antagonists
Interactions
δ-opioid receptors have been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116329 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050511 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ Alvimopan
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- ^ "Study of Antidepressant Efficacy of a Selective, High Affinity Enkephalinergic Agonist in Anxious Major Depressive Disorder (AMDD) - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. 10 October 2012. Retrieved 2015-12-11.
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Further reading
- Narita M, Funada M, Suzuki T (Jan 2001). "Regulations of opioid dependence by opioid receptor types". Pharmacology & Therapeutics. 89 (1): 1–15. PMID 11316510.
- Evans CJ, Keith DE, Morrison H, Magendzo K, Edwards RH (Dec 1992). "Cloning of a delta opioid receptor by functional expression". Science. 258 (5090): 1952–5. PMID 1335167.
- Offermanns S, Schultz G, Rosenthal W (Feb 1991). "Evidence for opioid receptor-mediated activation of the G-proteins, Go and Gi2, in membranes of neuroblastoma x glioma (NG108-15) hybrid cells". The Journal of Biological Chemistry. 266 (6): 3365–8. PMID 1671672.
- Simonin F, Befort K, Gavériaux-Ruff C, Matthes H, Nappey V, Lannes B, Micheletti G, Kieffer B (Dec 1994). "The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain". Molecular Pharmacology. 46 (6): 1015–21. PMID 7808419.
- Befort K, Mattéi MG, Roeckel N, Kieffer B (Mar 1994). "Chromosomal localization of the delta opioid receptor gene to human 1p34.3-p36.1 and mouse 4D bands by in situ hybridization". Genomics. 20 (1): 143–5. PMID 8020949.
- Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR (1994). "Identification of a human delta opioid receptor: cloning and expression". Life Sciences. 54 (25): PL463-9. PMID 8201839.
- Georgoussi Z, Carr C, Milligan G (Jul 1993). "Direct measurements of in situ interactions of rat brain opioid receptors with the guanine nucleotide-binding protein Go". Molecular Pharmacology. 44 (1): 62–9. PMID 8393523.
- Bzdega T, Chin H, Kim H, Jung HH, Kozak CA, Klee WA (Oct 1993). "Regional expression and chromosomal localization of the delta opiate receptor gene". Proceedings of the National Academy of Sciences of the United States of America. 90 (20): 9305–9. PMID 8415697.
- Ho MK, Wong YH (Jun 1997). "Functional role of amino-terminal serine16 and serine27 of G alphaZ in receptor and effector coupling". Journal of Neurochemistry. 68 (6): 2514–22. S2CID 24703413.
- Hedin KE, Bell MP, Kalli KR, Huntoon CJ, Sharp BM, McKean DJ (Dec 1997). "Delta-opioid receptors expressed by Jurkat T cells enhance IL-2 secretion by increasing AP-1 complexes and activity of the NF-AT/AP-1-binding promoter element". Journal of Immunology. 159 (11): 5431–40. PMID 9548483.
- Jordan BA, Devi LA (Jun 1999). "G-protein-coupled receptor heterodimerization modulates receptor function". Nature. 399 (6737): 697–700. PMID 10385123.
- Petaja-Repo UE, Hogue M, Laperriere A, Walker P, Bouvier M (May 2000). "Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor". The Journal of Biological Chemistry. 275 (18): 13727–36. S2CID 8293320.
- Gelernter J, Kranzler HR (Jul 2000). "Variant detection at the delta opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence". Human Genetics. 107 (1): 86–8. PMID 10982041.
- Guo J, Wu Y, Zhang W, Zhao J, Devi LA, Pei G, Ma L (Nov 2000). "Identification of G protein-coupled receptor kinase 2 phosphorylation sites responsible for agonist-stimulated delta-opioid receptor phosphorylation". Molecular Pharmacology. 58 (5): 1050–6. PMID 11040053.
- Gomes I, Jordan BA, Gupta A, Trapaidze N, Nagy V, Devi LA (Nov 2000). "Heterodimerization of mu and delta opioid receptors: A role in opiate synergy". The Journal of Neuroscience. 20 (22): RC110. PMID 11069979.
- Xu W, Chen C, Huang P, Li J, de Riel JK, Javitch JA, Liu-Chen LY (Nov 2000). "The conserved cysteine 7.38 residue is differentially accessible in the binding-site crevices of the mu, delta, and kappa opioid receptors". Biochemistry. 39 (45): 13904–15. PMID 11076532.
- Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. PMID 11076863.
- Saeed RW, Stefano GB, Murga JD, Short TW, Qi F, Bilfinger TV, Magazine HI (Dec 2000). "Expression of functional delta opioid receptors in vascular smooth muscle". International Journal of Molecular Medicine. 6 (6): 673–7. PMID 11078827.
- Xiang B, Yu GH, Guo J, Chen L, Hu W, Pei G, Ma L (Feb 2001). "Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization". The Journal of Biological Chemistry. 276 (7): 4709–16. S2CID 84945988.
- Yeo A, Samways DS, Fowler CE, Gunn-Moore F, Henderson G (Mar 2001). "Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells". Journal of Neurochemistry. 76 (6): 1688–700. S2CID 2755275.
External links
- "Opioid Receptors: δ". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2014-02-23. Retrieved 2007-07-23.
- delta+Opioid+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)