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 analgesia, perhaps as significant potentiators of μ-opioid receptor agonists. However, it seems like delta agonism provides heavy potentiation to any mu agonism. Therefore, even selective mu agonists can cause analgesia under the right conditions, whereas under others can cause none whatsoever.[7][8] It is also suggested however that the pain modulated by the μ-opioid receptor and that modulated by the δ-opioid receptor are distinct types, with the assertion that DOR modulates the nociception of chronic pain, while MOR modulates acute pain.[9]
Evidence for whether delta agonists produce respiratory depression is mixed; high doses of the delta agonist peptide DPDPE produced respiratory depression in sheep.[10] In contrast both the peptide delta agonist Deltorphin II and the non-peptide delta agonist (+)-BW373U86 actually stimulated respiratory function and blocked the respiratory depressant effect of the potent μ-opioid agonist alfentanil, without affecting pain relief.[11] It thus seems likely that while δ-opioid agonists can produce respiratory depression at very high doses, at lower doses they have the opposite effect, a fact that may make mixed mu/delta agonists such as DPI-3290 potentially very useful drugs that might be much safer than the μ agonists currently used for pain relief. Many delta agonists may also cause seizures at high doses, although not all delta agonists produce this effect.[12]
Of additional interest is the potential for delta agonists to be developed for use as a novel class of antidepressant drugs, following robust evidence of both antidepressant effects[13] and also upregulation of BDNF production in the brain in animal models of depression.[14] These antidepressant effects have been linked to endogenous opioid peptides acting at δ- and μ-opioid receptors,[15] and so can also be produced by enkephalinase inhibitors such as RB-101.[16] However, in human models the data for antidepressant effects remains inconclusive. In the 2008 Phase 2 clinical trial by Astra Zeneca, NCT00759395, 15 patients were treated with the selective delta agonist AZD 2327. The results showed no significant effect on mood suggesting that δ-opioid receptor modulation might not participate in the regulation of mood in humans. However, doses were administered at low doses and the pharmacological data also remains inconclusive.[17][18] Further trials are required.
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.[19] While this is exciting, rebuttal by the Javitch and coworkers suggest the idea of oligomerization may be overplayed. Relying on RET, Javitch and coworkers showed that RET signals were more characteristic of random proximity between receptors, rather than an actual bond formation between receptors, suggesting that discrepancies in binding profiles may be the result of downstream interactions, rather than novel effects due to oligomerization.[20] Nevertheless, coexpression of receptors remains unique and potentially useful in the treatment of mood disorders and pain.
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
A showing of selective delta opioid ligands. Blue represents a common phenolic moiety, yellow a basic nitrogen, and red a diethyl amide moiety which is not set in stone, but rather a bulky region that fits into a hydrophobic pocket.
^Clapp JF, Kett A, Olariu N, Omoniyi AT, Wu D, Kim H, et al. (February 1998). "Cardiovascular and metabolic responses to two receptor-selective opioid agonists in pregnant sheep". American Journal of Obstetrics and Gynecology. 178 (2): 397–401. doi:10.1016/S0002-9378(98)80032-X. PMID9500506.
^Jutkiewicz EM, Baladi MG, Folk JE, Rice KC, Woods JH (June 2006). "The convulsive and electroencephalographic changes produced by nonpeptidic delta-opioid agonists in rats: comparison with pentylenetetrazol". The Journal of Pharmacology and Experimental Therapeutics. 317 (3): 1337–1348. doi:10.1124/jpet.105.095810. PMID16537798. S2CID21838231.
^Hudzik TJ, Maciag C, Smith MA, Caccese R, Pietras MR, Bui KH, et al. (July 2011). "Preclinical pharmacology of AZD2327: a highly selective agonist of the δ-opioid receptor". The Journal of Pharmacology and Experimental Therapeutics. 338 (1): 195–204. doi:10.1124/jpet.111.179432. PMID21444630. S2CID10313748.
^Guo L, Zhang L, Zhang DC (October 2005). "[Mechanisms of delta-opioids cardioprotective effects in ischemia and its potential clinical applications]". Sheng Li Ke Xue Jin Zhan [Progress in Physiology] (in Chinese). 36 (4): 333–336. PMID16408774.
^Calderon SN, Rothman RB, Porreca F, Flippen-Anderson JL, McNutt RW, Xu H, et al. (July 1994). "Probes for narcotic receptor mediated phenomena. 19. Synthesis of (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- methoxybenzyl]-N,N-diethylbenzamide (SNC 80): a highly selective, nonpeptide delta opioid receptor agonist". Journal of Medicinal Chemistry. 37 (14): 2125–2128. doi:10.1021/jm00040a002. PMID8035418.
^Calderon SN, Rice KC, Rothman RB, Porreca F, Flippen-Anderson JL, Kayakiri H, et al. (February 1997). "Probes for narcotic receptor mediated phenomena. 23. Synthesis, opioid receptor binding, and bioassay of the highly selective delta agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide (SNC 80) and related novel nonpeptide delta opioid receptor ligands". Journal of Medicinal Chemistry. 40 (5): 695–704. doi:10.1021/jm960319n. PMID9057856.
^Jutkiewicz EM (June 2006). "The antidepressant -like effects of delta-opioid receptor agonists". Molecular Interventions. 6 (3): 162–169. doi:10.1124/mi.6.3.7. PMID16809477.
^Portoghese PS, Sultana M, Takemori AE (January 1988). "Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist". European Journal of Pharmacology. 146 (1): 185–186. doi:10.1016/0014-2999(88)90502-X. PMID2832195.
^Le Bourdonnec B, Windh RT, Ajello CW, Leister LK, Gu M, Chu GH, et al. (October 2008). "Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859)". Journal of Medicinal Chemistry. 51 (19): 5893–5896. doi:10.1021/jm8008986. PMID18788723.
^Onali P, Dedoni S, Olianas MC (January 2010). "Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics. 332 (1): 255–265. doi:10.1124/jpet.109.159939. PMID19828880. S2CID18893305.
^ abKathmann M, Flau K, Redmer A, Tränkle C, Schlicker E (February 2006). "Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 372 (5): 354–361. doi:10.1007/s00210-006-0033-x. PMID16489449. S2CID4877869.
^ abcTakayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, et al. (April 2002). "Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands". Journal of Medicinal Chemistry. 45 (9): 1949–1956. doi:10.1021/jm010576e. PMID11960505.
^Whistler JL, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P, et al. (July 2002). "Modulation of postendocytic sorting of G protein-coupled receptors". Science. 297 (5581): 615–620. doi:10.1126/science.1073308. PMID12142540. S2CID1219372.
Further reading
Narita M, Funada M, Suzuki T (January 2001). "Regulations of opioid dependence by opioid receptor types". Pharmacology & Therapeutics. 89 (1): 1–15. doi:10.1016/S0163-7258(00)00099-1. PMID11316510.
Simonin F, Befort K, Gavériaux-Ruff C, Matthes H, Nappey V, Lannes B, et al. (December 1994). "The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain". Molecular Pharmacology. 46 (6): 1015–1021. PMID7808419.
Befort K, Mattéi MG, Roeckel N, Kieffer B (March 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): 143–145. doi:10.1006/geno.1994.1146. PMID8020949.
Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, et al. (1994). "Identification of a human delta opioid receptor: cloning and expression". Life Sciences. 54 (25): PL463 –PL469. doi:10.1016/0024-3205(94)90138-4. PMID8201839.
Georgoussi Z, Carr C, Milligan G (July 1993). "Direct measurements of in situ interactions of rat brain opioid receptors with the guanine nucleotide-binding protein Go". Molecular Pharmacology. 44 (1): 62–69. PMID8393523.
Gelernter J, Kranzler HR (July 2000). "Variant detection at the delta opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence". Human Genetics. 107 (1): 86–88. doi:10.1007/s004390050016. PMID10982041.
Guo J, Wu Y, Zhang W, Zhao J, Devi LA, Pei G, et al. (November 2000). "Identification of G protein-coupled receptor kinase 2 phosphorylation sites responsible for agonist-stimulated delta-opioid receptor phosphorylation". Molecular Pharmacology. 58 (5): 1050–1056. doi:10.1124/mol.58.5.1050. PMID11040053.
Xu W, Chen C, Huang P, Li J, de Riel JK, Javitch JA, et al. (November 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): 13904–13915. doi:10.1021/bi001099p. PMID11076532.
Yeo A, Samways DS, Fowler CE, Gunn-Moore F, Henderson G (March 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): 1688–1700. doi:10.1046/j.1471-4159.2001.00185.x. PMID11259487. S2CID2755275.
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.
Amir Reza Khadem Anggota Parlemen IranMasa jabatan28 Mei 2004 – 28 Mei 2008Daerah pemilihanTehran, Rey, Shemiranat dan EslamshahrMayoritas693.603[1] Informasi pribadiLahirAmir Reza Khadem Azghadi10 Februari 1970 (umur 54)Mashhad, Negara Kekaisaran IranPartai politikIndependenOrang tuaMohammad Khadem (ayah)KerabatRasoul Khadem (saudara)Alma materUniversitas Shahid BeheshtiKarier olahragaNegara IranOlahragaGulat Rekam medali Gulat gaya bebas putra Permainan Olimpiade 1…
List of countries ranked by ethnic and cultural diversity level. List based on Fearon's analysis This article contains lists of countries ranked by ethnic and cultural diversity level. Methodology The lists are commonly used in economics literature to compare the levels of ethnic, cultural, linguistic and religious fractionalization in different countries.[1][2] Fractionalization is the probability that two individuals drawn randomly from the country's groups are not from the sam…
Moshe KahlonLahir19 November 1960 (umur 63)Tempat lahirHadera, IsraelKnesset16, 17, 18, 20Faksi yang diwakili di Knesset2003–2013Likud2015–2016KulanuJabatan menteri2009–2013Menteri Komunikasi2011–2013Menteri Kesejahteraan & Pelayanan Sosial2015–Menteri Keuangan2016Menteri Perlindungan Lingkungan Hidup2016–2017Menteri Ekonomi Moshe Kahlon (Ibrani: משה כחלון, lahir 19 November 1960) adalah seorang politikus Israel yang menjabat sebagai anggota Knesset untuk Likud, dan …
Hostility, prejudice, or discrimination against Slavic peoples Part of a series onDiscrimination Forms Institutional Structural Attributes Age Caste Class Dialect Disability Genetic Hair texture Height Language Looks Mental disorder Race / Ethnicity Skin color Scientific racism Rank Sex Sexual orientation Species Size Viewpoint Social Arophobia Acephobia Adultism Anti-albinism Anti-autism Anti-homelessness Anti-drug addicts Anti-intellectualism Anti-intersex Anti-left handedness Anti-Ma…
Irish politician and activist For other people named Richard Martin, see Richard Martin (disambiguation). Richard MartinMember of Parliamentfor County GalwayIn office1818–1826Serving with James DalyMember of Parliamentfor County GalwayIn office1801–1812Serving with Richard Le Poer Trench 1801–1805Denis Bowes Daly 1805–1812Member of Parliamentfor County GalwayIn office1800–1801Member of Parliamentfor LanesboroughIn office1798–1800Member of Parliamentfor JamestownIn off…
Amelia Bingham ca. 1903 Amelia Swilley Bingham (20 Maret 1869 – 1 September 1927)[1] adalah seorang aktris Amerika serikat yang berasal dari Hicksville, Ohio.[2] Karirnya di Broadway diperpanjang dari tahun 1896 sampai 1926[1] Bingham kuliah di Ohio Wesleyan University sebelum menikah dengan Lloyd Bingham. Ayahnya adalah seorang pendeta Metodis yang mengelola sebuah hotel. Calon suaminya membujuk ayahnya untuk mengizinkan Bingham naik panggung kira-kira se…
Syafruddin PrawiranegaraSyafruddin pada 1960-an Ketua Pemerintahan Darurat Republik IndonesiaSetingkat Presiden dan Perdana Menteri Republik Indonesia[a]Masa jabatan19 Desember 1948 – 14 Juli 1949 PendahuluSukarnoPenggantiSukarno[b]Wakil Perdana Menteri Indonesia ke-3Masa jabatan4 Agustus 1949 – 20 Desember 1949PresidenSukarnoPerdana MenteriMohammad Hatta PendahuluAdenan Kapau GaniSetyadjit SoegondoRaden SjamsoeddinWondoamisenoPenggantiAbdul Hakim Haraha…
Voce principale: AIDS. Storia della pandemia di AIDSepidemiaPatologiaAIDS Origine Kinshasa Periodo1981[1] -in corso Dati statistici globali[2]Numero di casi37,9 milioni (2018) Numero di morti32 milioni (2018[3]) Modifica dati su Wikidata · Manuale Francobollo bielorusso col nastro rosso, simbolo della lotta all'AIDS e della solidarietà alle vittime e ai sieropositivi La storia della diffusione dell'AIDS su scala pandemica (o epidemia globale) …
Voce principale: Football Club Turris 1944. Associazione Calcio TurrisStagione 1978-1979Sport calcio Squadra Turris Allenatore Nicola Chiricallo, poi Giulio Lopez Presidente Salvatore Gaglione Serie C1 - Gir. B14º posto Coppa Italia SemiproFase eliminatoria a gironi Maggiori presenzeCampionato: Strino (34) Miglior marcatoreCampionato: Barone (10) 1977-1978 1979-1980 Si invita a seguire il modello di voce Turris 1978-79 Questa voce raccoglie le informazioni riguardanti l'Associazione Ca…
Synagogue de la Ghriba Salle de prière de la synagogue de la Ghriba. Présentation Nom local كنيس الغريبة Culte Judaïsme(Maghrebim) Type Synagogue Géographie Pays Tunisie Gouvernorat Médenine Localité Erriadh Coordonnées 33° 48′ 50″ nord, 10° 51′ 33″ est modifier La synagogue de la Ghriba (arabe : كنيس الغريبة) est une synagogue tunisienne qui constitue l'un des principaux marqueurs identitaires des Juifs de Djerba, l…
Jimmy Neutron: Boy GeniusSutradaraJohn A. DavisProduserSteve Oedekerk, John A. Davis, Albie HechtSkenarioJohn A. Davis, Steve Oedekerk, J. David Stern, David N. WeissCerita John A. Davis Steve Oedekerk Pemeran Debi Derryberry Patrick Stewart Martin Short Rob Paulsen Jeffrey Garcia Carolyn Lawrence Crystal Scales Candi Milo Penata musikJohn DebneyPenyunting Gregory Perler Jon Price Perusahaanproduksi Nickelodeon Movies O Entertainment DNA Productions DistributorParamount PicturesTanggal ril…
Aircraft designed to protect other aircraft The North American P-51 Mustang is one of the best-known escort fighters of World War II. The escort fighter was a concept for a fighter aircraft designed to escort bombers to and from their targets. An escort fighter needed range long enough to reach the target, loiter over it for the duration of the raid to defend the bombers, and return. A number of twin-engined heavy fighters with high fuel capacity were designed for escort duties prior to the outb…
This article is about the reasons why the Eighty Years' War broke out. For how the Eighty Years' War has been seen after it started, and debates between historians how to write about the war, see Historiography of the Eighty Years' War. The origins of the Eighty Years' War are complicated, and have been a source of disputes amongst historians for centuries.[1] The Habsburg Netherlands emerged as a result of the territorial expansion of the Burgundian State in the 14th and 15th centuries.…
Spaceflight where spacecraft orbits an astronomical body This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Orbital spaceflight – news · newspapers · books · scholar · JSTOR (March 2008) (Learn how and when to remove this message) Space Shuttle Discovery rockets to orbital velocity, seen here just after booster se…
Melayu Malaysiaملايو مليسياDaerah dengan populasi signifikanMalaysiaBahasaMelayuAgamaMayoritas Sunni bermazhab Syafi'i.Kelompok etnik terkaitMelayu Indonesia, Melayu Thai, Melayu Singapura, Melayu Brunei. Orang Melayu Malaysia Masyarakat Melayu (bahasa Melayu: Melayu Malaysia; Jawi: ملايو مليسيا) adalah salah satu komponen dari bangsa Malaysia. Kebanyakan adalah penduduk setempat yang telah menghuni wilayah Semenanjung Tanah Melayu dan Pulau Borneo bagian barat laut. Ma…
Pour les articles homonymes, voir Globe. The Globe and Mail Pays Canada Langue Anglais Périodicité Quotidienne Format Grand format Prix au numéro 4,00 $ CA (la semaine) 7,00 $ CA (le samedi) Fondateur George Brown Date de fondation 1844 Ville d’édition Toronto Propriétaire The Globe and Mail Inc.Woodbridge (100 %) Rédacteur en chef Edward Greenspon ISSN 0319-0714 Site web www.theglobeandmail.com modifier The Globe and Mail est un journal canadien quotidien de langue …
Artikel ini bukan mengenai Raga rock.Artikel ini membutuhkan rujukan tambahan agar kualitasnya dapat dipastikan. Mohon bantu kami mengembangkan artikel ini dengan cara menambahkan rujukan ke sumber tepercaya. Pernyataan tak bersumber bisa saja dipertentangkan dan dihapus.Cari sumber: Reggae rock – berita · surat kabar · buku · cendekiawan · JSTOR (October 2012)Reggae rockPepper tampil di Vans Warped Tour, pada 3 Agustus 2007.Sumber aliranReggaerokreggae f…
يفتقر محتوى هذه المقالة إلى الاستشهاد بمصادر. فضلاً، ساهم في تطوير هذه المقالة من خلال إضافة مصادر موثوق بها. أي معلومات غير موثقة يمكن التشكيك بها وإزالتها. (ديسمبر 2018) 30° خط طول 30 شرق خريطة لجميع الإحداثيات من جوجل خريطة لجميع الإحداثيات من بينغ تصدير جميع الإحداثيات من كيه …
Taiwanese manufacturer This article includes a list of general references, but it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (July 2008) (Learn how and when to remove this message) Inventec CorporationNative name英業達公司Company typePublicTraded asTWSE: 2356IndustryComputer hardwareFounded1975; 49 years ago (1975)HeadquartersTaipei, TaiwanRevenue$7.2 billion USD (2006)Operating income8,184,46…
