Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [72]) are activated by the endogenous ligands prostaglandins PGD₂, PGE₁, PGE₂ , PGF_2α, PGH₂, prostacyclin [PGI₂] and thromboxane A₂. Measurement of the potency of PGI₂ and thromboxane A₂ is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies.

Whilst cicaprost is selective for IP receptors, it does exhibit moderate agonist potency at EP₄ receptors [1]. Apart from IP receptors, iloprost also binds to EP₁ receptors.

The EP₁ agonist 17-phenyl-ω-trinor-PGE₂ also shows agonist activity at EP₃ and EP₄ receptors [15,60]. Butaprost and SC46275 may require de-esterification within tissues to attain full agonist potency. There is evidence for subtypes of FP [30] and TP receptors [27,42]. mRNA for the EP₃ receptor undergoes alternative splicing to produce variants which can interfere with signalling [41] or generate complex patterns of G-protein (G_i/o, G_q/11, G_s and G_12,13) coupling (e.g. [26,40]). The number of EP₃ receptor (protein) variants are variable depending on species, with five in human, three in rat and three in mouse. Putative receptor(s) for prostamide F (which as yet lack molecular correlates) and which preferentially recognize PGF2-1-ethanolamide and its analogues (e.g. Bimatoprost) have been identified, together with moderate-potency antagonists (e.g. AGN 211334) [71].

The free acid form of AL-12182, AL12180, used in in vitro studies, has a EC₅₀ of 15nM which is the concentration of the compound giving half-maximal stimulation of inositol phosphate turnover in HEK-293 cells expressing the human FP receptor [47].

References given alongside the TP receptor agonists I-BOP [36] and STA₂ [6] use human platelets as the source of TP receptors for competition radio-ligand binding assays to determine the indicated activity values.

Pharmacological evidence for a second IP receptor, denoted IP₂, in the central nervous system [59,66] and in the BEAS-2B human airway epithelial cell line [70] is available. This receptor is selectively activated by 15R-17,18,19,20-tetranor-16-m-tolyl-isocarbacyclin (15R-TIC) and 15R-Deoxy 17,18,19,20-tetranor-16-m-tolyl-isocarbacyclin (15-deoxy-TIC). However, molecular biological evidence for an IP₂ subtype is currently lacking.

* Key recommended reading is highlighted with an asterisk

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Subcommittee members: Xavier Norel (Chairperson) INSERM U1148 Laboratory for Vascular Translational Science (LVTS) Bichat-Claude Bernard Hospital 46, rue Henri Huchard 75877 Paris Cedex 18 France Lucie Clapp Professor of Vascular Physiology Institute of Cardiovascular Science Floor 3, Rayne Building University College London 5 University Street London, WC1E 6JF Akos Heinemann Otto Loewi Research Center (for Vascular Biology, Immunology and Inflammation) Division of Pharmacology Lehrstuhlinhaber/Lehrstuhlinhaberin Universitätsplatz 4 8010 Graz Yukihiko Sugimoto, Ph.D. Department of Pharmaceutical Biochemistry Graduate School of Pharmaceutical Sciences Kumamoto University 5-1, Oe-Honmachi, Chuo-ku Kumamoto 862-0973 JAPAN Chengcan Yao Edinburgh Medical School: Clinical Sciences Centre for Inflammation Research University of Edinburgh, UK

Other contributors: Richard M. Breyer Department of Medicine Vanderbilt University School of Medicine Nashville TN USA Robert A. Coleman Pharmagene Laboratories 2A Orchard Road Royston SG8 5HD UK Mark Giembycz Snyder Institute for Chronic Diseases Health Research Innovation Centre 4AA08 3280 Hospital Drive NW Calgary, T2N 4N1 AB Canada Rebecca Hills (Past curator) Robert L. Jones Strathclyde Institude of Pharmacy and Biomedical Sciences University of Strathclyde The John Arbuthnott Building 27 Taylor Street Glasgow G4 0NR UK Shuh Narumiya Department of Pharmacology Kyoto University Faculty of Medicine Yoshida Sakyo-ku Kyoto 606 Japan Roy Pettipher Atopix Therapeutics Ltd The Innovation Centre 99 Park Drive Milton Park Abingdon UK David F. Woodward Biological Sciences Allergan PO Box 19534 2525 Dupont Drive Irvine CA 92713-9534 USA