Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Pharmacological Reviews
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Pharmacological Reviews

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit Pharm Rev on Facebook
  • Follow Pharm Rev on Twitter
  • Follow ASPET on LinkedIn
Research ArticleIUPHAR Nomenclature Reports

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

D. F. Woodward, R. L. Jones and S. Narumiya
Pharmacological Reviews September 2011, 63 (3) 471-538; DOI: https://doi.org/10.1124/pr.110.003517
D. F. Woodward
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. L. Jones
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Narumiya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Fig. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 1.

    Deduced amino sequence of human prostanoid receptors, in alignment. Amino acid residues with 100% homology between all receptors are highlighted in green. Amino acid residues with complete homology, except for DP2, are highlighted in blue.

  • Fig. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 2.

    Structures of agonists for prostanoid DP1 and DP2 receptors. PGD2, the most active natural agonist, is shown in the circle. Promotion of DP2-selectivity mainly involves alterations to C15; α indicates natural 2-series side-chain. a, ring system related to 6β-PGI1. b, PGI2 analog with unnatural ring chirality. c, EP1 and EP2 agonism retained. d, some EP2 agonism remains. e, PGH2 analog with unnatural ring chirality. f, 14-cis isomer is major component.

  • Fig. 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 3.

    Structures of representative DP1 and DP2 (CRTH2) antagonists.

  • Fig. 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 4.

    Structures of agonists for prostanoid EP receptor subtypes. PGE2, the most active natural agonist, is shown in the circle. 17-Phenyl PGE2 and sulprostone have modest EP1/EP3 and EP3/EP1 selectivities, respectively. CP-533536 and compound 9 are EP2 agonists with nonprostanoid structures. a, Belley et al. (2005). b, Shimazaki et al. (2000). c, Blovin et al. (2010).

  • Fig. 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 5.

    Structures of representative EP1, EP3, and EP4 receptor antagonists. Heterocycle substitution in DG-041 maintains high EP3 affinity (Hategan et al., 2009).a, Asada et al. (2010). ONO-AE3-240, T. Maruyama, personal communication.

  • Fig. 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 6.

    Structures of agonists for the prostanoid FP receptor and the corresponding prostamide F receptor. PGF2α potently activates both receptors, whereas its C1-ethanolamide activates only the prostamide F receptor. a, partial agonist.

  • Fig. 7.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 7.

    Structures of FP antagonists and the prostamide antagonist (AGN 211334).

  • Fig. 8.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 8.

    Structures of agonists for the prostanoid IP receptor. PGI2 (prostacyclin), the most active natural agonist, is shown in the circle. The diphenyl-heteroatomic unit critical to IP agonism in nonprostacyclin mimetics of prostacyclin is shown in blue. a, partial agonist. b, prodrug for MRE-269.

  • Fig. 9.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 9.

    Structures of IP receptor antagonists.

  • Fig. 10.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 10.

    Structures of agonists for the prostanoid TP receptor. TxA2 and PGH2, the most active natural agonists, are shown in the circle. Only structural alterations relative to PGH2 and TxA2 are illustrated in the figure. The vertical bracket indicates the presence of 2-series α- and ω-chains. a, partial agonist.

  • Fig. 11.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 11.

    Structures of representative antagonists for the prostanoid TP receptor.

Tables

  • Figures
    • View popup
    TABLE 1

    Primary G protein coupling for prostanoid receptors

    Prostanoid Receptor SubtypeProstanoid Molecular Evolution ClusterG ProteinSecond Messenger
    DP11Gs↑ cAMP
    EP12↑ [Ca2+]i
    EP21Gs↑ cAMP
    EP33Gi↓ cAMP
    EP41Gs↑ cAMP
    FP2Gq↑ [Ca2+]i PI turnover
    IP1Gs↑ cAMP
    TP2Gq↑ [Ca2+]i PI turnover
    • View popup
    TABLE 2

    Potential therapeutic application of DP1 agonists

    DP1 AgonistRouteDoseSpeciesExperimental ModelIndicationReference
    572C85 192C86Topical2–250 μgRabbit, catIntraocular pressureGlaucomaMatsugi et al., 1995
    AL-6598Topical0.01%MonkeyIntraocular pressureGlaucomaToris et al., 2006
    BW 245CIntrathecal83 ng/kg (IC50)MouseNociceptin-induced allodyniaChronic painMinami et al., 1997
    BW 245CTopical2.5 μgRabbitIntraocular pressureGlaucomaGoh et al., 1988
    BW 245CTopical50 μMMouseEpicutaneous sensitization to OVAAtopic dermatitisAngeli et al., 2004
    BW 245CIntratracheal100 μMMouseOVA-alum asthmaAsthmaHammad et al., 2007
    BW 245C1–1000 nMRatCell/tissue cultureNeurodegenerative diseasesLiang et al., 2005b
    BW 245CIn vitro+ (−/− DP1 mice)0.05–5 μMMouseIschemia-reperfusion injuryCerebral ischemic disordersSaleem et al., 2007b
    BW 245CTopical0.01–1%RabbitIntraocular pressureGlaucomaWoodward et al., 1990
    BW 245C AS 702224IntracavernosalBW 245C, 59 nM; AS 702224, 29 nM (EC50 in isolated human tissue)Rabbit, rat, human cavernosal tissuePenile tumescenceErectile dysfunctionBrugger et al., 2008
    SQ-27986Topical2.5–25 μgRabbitIntraocular pressureGlaucomaWoodward et al., 1993
    SQ-27986Topical1–30 μgMonkeyIntraocular pressureGlaucomaCrawford et al., 1992
    TS-022Topical2.5 → 250 nMMouseNC/Nga miceAtopic dermatitisArai et al., 2007
    • AL-6598, 2-[[(2Z)-4-[(1R,2R,3R,5R)-5-chloro-2-[(3R)-3-cyclohexyl-3- hydroxypropyl]-3-hydroxycyclopentyl]-2-buten-1-yl]oxy]-1-methylethyl ester, acetic acid.

    • View popup
    TABLE 3

    Potential therapeutic application DP1 antagonists

    DP1 AntagonistRouteDoseSpeciesExperimental ModelIndicationReference
    LaropiprantOral37.5 → 300 mg (human dose)Mice, humansNA-induced cutaneous vasodilation in miceAdjunctive therapy for dyslipidemiaCheng et al., 2006; Paolini et al., 2009
    S-5751Oral30 mg/kgSheepAscaris suum-induced asthmaasthmaShichijo et al., 2009
    • NA, nicotinic acid.

    • View popup
    TABLE 4

    Potential therapeutic application of EP1 antagonists

    EP1 AntagonistsRouteDoseSpeciesExperimental ModelIndicationReference
    ONO-8711Intravenous1 and 3 mg/kgRatAcetic acid-induced inflammationBladder inflammationIkeda et al., 2006
    ONO-8711Dietary400 or 800 ppmRatPhIP-induced breast cancerBreast cancerKawamori et al., 2001a,b
    ONO-8711Dietary250, 500, 1000 ppmMouseAzoxymethane-induced aberrant crypt foci, Min miceColon cancerWatanabe et al., 1999
    ONO-8713Oral20 mg/kgMouseDNFB contact sensitivityContact dermatitisNagamachi et al., 2007
    ONO-8713Topical50 μgMouseUVB-induced inflammation and tumor formationSunburn, skin cancerTober et al., 2006
    ONO-8713Dietary250, 500 1000 ppmMouseAzoxymethane-induced aberrant crypt fociColon cancerWatanabe et al., 2000
    ONO-8713Intraventricular0–1–10 nMMouseNMDA excitotoxicityStrokeAhmad et al., 2006a
    ONO-8713Intraperitoneal10 mg/kgMouseCerebral artery occlusionStrokeAhmad et al., 2006a
    ONO-8713Intrathecal1 or 10 nmolMouseNeurochemical allodyniaPainTsukamoto et al., 2010
    PF-2907617-02Intravenous1 mg/kgRatBalloon catheter-induced bladder outlet obstructionOveractive bladder syndromeLee et al., 2007a,b
    SC-51089Intraperitoneal25 mg/kgMiceKMG4 tumor xenografts on SCID miceGliomaMatsuo et al., 2004
    SC-51089Intraperitoneal10 mg/kgRatLithium-pilocarpine status epilepticusEpilepsyPekcec et al., 2009
    SC-51322Oral10 mg/kgRatSpontaneously hypertensive ratHypertensionGuan et al., 2007
    • PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; SC-51089, dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-(1-oxo-3-(4-pyridinyl)propyl)hydrazide, monohydrochloride.

    • View popup
    TABLE 5

    Potential therapeutic application of EP2 agonists

    AgonistRouteDoseSpeciesExperimental ModelIndicationReference
    AH 13205Aerosol0.1–3 nMGuinea pigsHistamine induced bronchoconstrictionAsthmaNials et al., 1993
    ButaprostTissue culture vs. oxytocin10−6 M infusionHumanIsolated human uterine specimens from pregnant and nonpregnant donorsPrevention of preterm labor; dysmenorrhoeaDuckworth et al., 2002
    ButaprostTopical (ocular)0.1%MonkeyLaser-induced glaucomatous monkeyGlaucomaNilsson et al., 2006
    CP 533536Local implant10, 50, 100 mg/mlDogCanine ulnar critical defectFracture healingParalkar et al., 2003
    CP 533536Topical (ocular)0.01–0.1%Dog, monkeyLaser-induced glaucomatous monkeyGlaucomaWoodward and Chen, 2007
    • View popup
    TABLE 6

    Potential therapeutic application of EP3 agonists

    AgonistRouteDoseSpeciesExperimental ModelIndicationReference
    MB 28767Intravenous2 pmol · kg−1 · min−1PigOcclusion/reperfusionCardiac infarctionHohlfeld et al., 2000
    MB 28767Intracisternal1 fg–30 ng per animalMouseNaloxone-induced withdrawal jumpingOpiate withdrawal syndromeNakagawa et al., 1995
    ONO-AE-248Subcutaneous10 μg/kgMouseOvalbumin induced asthmaAsthmaKunikata et al., 2005
    TEI-3356Intravenous1 μg · kg−1 · h−1RatOcclusion/reperfusionCardiac infarctionZacharowski et al., 1999
    • TEI-3356, 5-(-7-hydroxy-6-(4-hydroxy-4-methyl-1-octenyl)bicyclo(3.3.0)oct-2-en-3-yl)pentanoic acid.

    • View popup
    TABLE 7

    Potential therapeutic application of EP3 antagonists

    AntagonistRouteDoseSpeciesExperimental ModelIndicationReference
    DG-041Intravenous10 mg/kgRatUrinary bladder distensionOveractive bladderSu et al., 2008a
    DG-041Oral0.1–100 mg/kgRatEx vivo platelet aggregation; bleeding timeAtherothrombosisSingh et al., 2009
    L-826266Intraperiaqueductal grey0.125 nM–0.5 nMMouseFormalin induced hyperalgesiaPainOliva et al., 2006
    L-826266Intraplantar3–30 nmolMousePaw-lickingRheumatoid arthritisKassuya et al., 2007
    ONO-AE3-240Subcutaneous3.30 mg/kgMouseHSV-1 inoculationPost-herpetic painTakasaki et al., 2005
    ONO-AE3-240Subcutaneous50 nmol/tumorMouseSarcoma 180 cell tumorCancerAmano et al., 2003
    • HSV-1, Herpes simplex virus 1.

    • View popup
    TABLE 8

    Potential therapeutic application of EP4 antagonists (inflammation/pain is reviewed in Jones et al., 2009)

    AgonistRouteDoseSpeciesExperimental ModelIndicationReference
    L 161982Intravitreal injection0.01–1 μMRatO2-retinopathy laser induced choroidal neovascularizationAge-related macular degenerationYanni et al., 2009
    ONO-AE2-227In diet100–400 ppmMouseAzoxymethane induced aberrant crypt foci; min mouseColon cancerMutoh et al., 2002
    ONO-AE3-208Oral10 mg/kgMouseInjection of M26 cellsColon cancerYang et al., 2006
    • View popup
    TABLE 9

    Potential therapeutic application of EP4 agonists

    AgonistRouteDoseSpeciesExperimental ModelIndicationReference
    3,7-Dithia PGE1 and its isopropyl esterTopical0.01–0.1%Monkey“Glaucomatous” monkey intraocular pressureGlaucomaWoodward et al., 2009
    4819-CDSubcutaneous0.3 mg/kgMouseIschemia-reperfusion injuryMyocardial infarctionXiao et al., 2004
    AEI-734ColitisKabashima et al., 2002
    AGN 205203 and its methyl esterSubcutaneous3 mg/kgMouseDextran sodium sulfate colitisColitisJiang et al., 2007
    CP-734432Subcutaneous0.3–3 mg/kgRatOvariectomized ratsOsteoporosisKe et al., 2006
    ONO-4819Subcutaneous10, 30 μg/kgRatFemoral drill-hole injuryBone fracture healing, osteoporosisTanaka et al., 2004
    ONO-4819Subcutaneous3, 30 μg/kgRatMechanical loading, to tibiaBone fracture, osteoporosisHagino et al., 2005
    ONO-4819Intravenous100 ng/kgRatOvariectomized ratOsteoporosisYoshida et al., 2002
    ONO-AE1-329Intracolonic25, 100 μg/kgRatDextran sodium sulfate colitisColitisNitta et al., 2002
    ONO-AE1-329Intravenous1–10 μg/kgRatIndomethacin-induced lesionsNSAID-induced gastrointestinal lesionsKunikata et al., 2002
    ONO-AE1-329Intraperitoneal0.1 mg/kgRatIndomethacin-induced lesionsNSAID-induced gastrointestinal lesionsHatazawa et al., 2006
    ONO-AE1-329Subcutaneous0.1–1000 ng/gRatNeonatal ductus arteriosus dilatationPremature birthMomma et al., 2005
    ONO-AE1-329Local gelatin plug1 mg/mlGuinea pigAuditory brain stem responseSensorineural hearing lossHori et al., 2009
    ONO-AE1-329Subcutaneous0.05, 0.5 mg/kg 55 μg daily infusion per animalMouseN2 receptor knockout miceNephrogenic diabetes insipidusLi et al., 2009
    ONO-AE1-329Subcutaneous100 μg/kgMouseAnti-glomerular basement membrane antibody nephritisGlomerulonephritisNagamatsu et al., 2006
    ONO-AE1-329Intravenous1–10 μg/kgRatEndotoxinSepticemiaSakamoto et al., 2004
    PF-04475270Topical0.002–0.1 mg/mlDogNormal dog intraocular pressureGlaucomaPrasanna et al., 2009
    • View popup
    TABLE 10

    Recently identified potential therapeutic application of TP antagonists

    AntagonistRouteDoseSpeciesExperimental ModelIndicationReference
    GR-32191 (vapiprost)Oral (drinking water)1 mg · kg−1 · day−1MouseSTZ diabetesDiabetic retinopathyWright et al., 2009
    KP-496Intratracheal30 and 100 μm/animalRatSephadex induced airway inflammationAsthmaIshimura et al., 2009
    KP-496Intranasal0.003–0.05%Guinea pigOvalbumin, Japanese cedar pollen allergyAllergic rhinitisMizutani et al., 2008
    ONO-3708Intradermal0.1 and 1 nmol/siteMouseTxA2-induced scratchingPruritusAndoh et al., 2007
    S18886 (terutroban)Oral10 and 30 mg/kgRatUninephrectomized obese Zucker ratsType 2 diabetesSebeková et al., 2007
    • STZ, streptozotocin; ONO-3708, (1S-(1α,2β(Z),3α(S*),5α))-7-(3-((cyclopentylhydroxyacetyl)amino)-6,6-dimethylbicyclo(3.1.1)hept-2-yl)-5-heptenoic acid.

    • View popup
    TABLE 11

    Therapeutic applications of DP2 antagonists

    DP2 antagonistRouteDoseSpeciesExperimental ModelIndicationReference
    mg/kg
    AM 156Oral10MouseSmoke exposureCOPDStebbins et al., 2010
    Compound 23Oral10MouseOvalbumin allergyAllergic rhinitisStearns et al., 2009
    Compound AOral10MouseFITC-cutaneous allergyAtopic dermatitisBoehme et al., 2009
    RamatrobanOral5MouseAllergic (ovalbumin) eosinophilic airway inflammationAsthmaUller et al., 2007
    RamatrobanOral30MouseCry J1-induced pollinosisAllergic rhinitisNomiya et al., 2008
    TM-30089Oral5MouseAllergic (ovalbumin) eosinophilic airway inflammationAsthmaUller et al., 2007
    • AM 156, (2′-((cyclopropanecarbonylethylamino)methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)acetic acid; COPD, chronic obstructive pulmonary disease; FITC, fluorescein isothiocyanate.

PreviousNext
Back to top

In this issue

Pharmacological Reviews: 63 (3)
Pharmacological Reviews
Vol. 63, Issue 3
1 Sep 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Pharmacological Reviews article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress
(Your Name) has forwarded a page to you from Pharmacological Reviews
(Your Name) thought you would be interested in this article in Pharmacological Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleIUPHAR Nomenclature Reports

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

D. F. Woodward, R. L. Jones and S. Narumiya
Pharmacological Reviews September 1, 2011, 63 (3) 471-538; DOI: https://doi.org/10.1124/pr.110.003517

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleIUPHAR Nomenclature Reports

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

D. F. Woodward, R. L. Jones and S. Narumiya
Pharmacological Reviews September 1, 2011, 63 (3) 471-538; DOI: https://doi.org/10.1124/pr.110.003517
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • I. Introduction
    • II. Receptor Types, Subtypes, and mRNA Splicing Variants
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PRRs in Health and Disease
  • Relaxin Family Peptide Receptors
  • Adhesion G Protein–Coupled Receptors
Show more IUPHAR Nomenclature Reports

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Pharmacological Reviews
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacology Research & Perspectives
ISSN 1521-0081 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics