Prostanoid Receptors

Prostanoid receptors are activated by the endogenous ligands prostaglandin (PG) D2, PGE2, PGF, PGH2, prostacyclin (PGI2) and thromboxane A2. Cyclooxygenase (COX) converts arachidonic acid to PGH2, from which the other prostaglandins are synthesized.

Products
Background
Literature
Gene Data

Agonists

Cat No Product Name / Activity
4180 Beraprost sodium
Potent prostacyclin IP receptor agonist
1442 BMY 45778
Non-prostanoid prostacyclin IP receptor partial agonist
2295 (±)-Cloprostenol sodium salt
Water-soluble PGF2α analog and potent FP receptor agonist
4027 16,16-Dimethyl Prostaglandin E2
Synthetic prostaglandin E2 (Cat. No. 2296) derivative; regulates HSC development
2989 Epoprostenol
Endogenous IP receptor agonist
4542 (+)-Fluprostenol
High affinity FP prostaglandin receptor agonist
2038 Iloprost
Prostacyclin (PGI2) analog
4757 Latanoprost
FP prostaglandin receptor agonist; also exhibits agonist activity at EP1 and EP3 receptors
2297 Misoprostol
Cytoprotective PGE1 analog
2296 Prostaglandin E2
Major endogenous prostanoid
4214 Prostaglandin F2α
Naturally-occurring prostanoid; potent vasoconstrictor
3351 Selexipag
Selective prostacyclin IP1 receptor agonist
3049 Sulprostone
EP3 and EP1 receptor agonist
4069 TCS 2510
Selective EP4 agonist
4218 Travaprost
Potent and selective FP prostaglandin receptor agonist
5349 Treprostinil
Potent prostacyclin (PGI2) analog
1932 U 46619
Potent, stable thromboxane A2 (TP) receptor agonist

Antagonists

Cat No Product Name / Activity
3025 AA 2414
Thromboxane A2 (TP) receptor antagonist
0671 AH 6809
EP1 and EP2 receptor antagonist
5701 AMG 853
Potent dual CRTH2 and prostaglandin D2 (PGD2) receptor antagonist
2732 BAY-u 3405
Dual TP/DP2 (CRTH2) receptor antagonist
5327 BGC 20-1531 hydrochloride
High affinity and selective EP4 antagonist
6240 DG 041
Potent and selective EP3 antagonist; antiplatelet and antithrombotic
5924 ER 819762
Potent EP4 receptor antagonist; orally bioavailable
4668 GW 627368
Selective EP4 receptor competitive antagonist
0836 ICI 185,282
Potent thromboxane receptor antagonist
0837 ICI 192,605
Potent thromboxane A2/TP receptor antagonist
2514 L-161,982
Selective EP4 receptor antagonist
1949 L-670,596
Potent, selective thromboxane A2/prostaglandin endoperoxide antagonist
3342 L-798,106
Potent and highly selective EP3 antagonist
5406 ONO 8130
EP1 receptor antagonist
3565 ONO AE3 208
High affinity and selective EP4 antagonist
4818 PF 04418948
Potent and selective EP2 receptor antagonist
4268 Ro 1138452 hydrochloride
Selective prostacyclin IP receptor antagonist
5568 S 18886
Potent thromboxane A2 (TP) antagonist
1206 SC 19220
Selective EP1 receptor antagonist
3758 SC 51089
Selective EP1 receptor antagonist
2791 SC 51322
Potent EP1 receptor antagonist
5052 TG 4-155
High affinity and selective EP2 receptor antagonist

Other

Cat No Product Name / Activity
1620 Alprostadil
Prostaglandin. Vasodilator and antiplatelet agent in vivo
2756 Arachidonic acid (in Tocrisolve™100)
Endogenous free fatty acid (in water-soluble emulsion)
1510 Ozagrel hydrochloride
Selective thromboxane A2 synthetase inhibitor

Related Targets

    Prostanoid receptors are activated by the endogenous ligands prostaglandin (PG) D2, PGE2, PGF, PGH2, prostacyclin (PGI2) and thromboxane A2. Cyclooxygenase (COX) converts arachidonic acid to PGH2, from which the other prostaglandins are synthesized. Prostanoid receptors are a family of nine G-protein-coupled receptors that have distinct tissue distributions and actions.

    1. DP receptors (DP1-2) are coupled to Gαs. They are expressed in the small intestine, lung, stomach and uterus. Activation of DP1 results in inhibition of platelet activation and vasodilation; they are also involved in sleep regulation. DP2 activation leads to immune cell activation.
    2. EP receptors (EP1-4) are a diverse group of prostanoid receptors. EP1 receptors are restricted to the kidney, lung and stomach, and induce smooth muscle contraction. EP2 and EP4 couple to Gαs and induce smooth muscle relaxation. EP3 is an inhibitory receptor that prevents smooth muscle relaxation.
    3. FP receptors are coupled to Gαq. They are abundant in the corpus luteum, where they are involved in luteolysis.
    4. IP receptors are coupled to Gαs and are involved in pain mediation, relaxation of vascular smooth muscle, inhibition of platelet aggregation and they contribute to cardiovascular health.
    5. TP receptors can be coupled to both Gαq and Gαi. They are expressed abundantly in highly vascular tissues such as the kidney and heart, and immune-related organs such as the thymus and spleen. They mediate smooth muscle contraction and platelet aggregation.

    External sources of pharmacological information for Prostanoid Receptors :

    Literature for Prostanoid Receptors

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    Cardiovascular Research Product Guide

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    Asthma Poster

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    Cardiovascular Poster

    Cardiovascular disease remains one of the major causes of morbidity and mortality in the Western world and therefore this therapeutic area continues to be of great interest to researchers. This poster highlights the key GPCRs regulating vascular reactivity.

    Pain

    Pain Poster

    Peripheral sensitization is the reduction in the threshold of excitability of sensory neurons that results in an augmented response to a given external stimulus. This poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described.

    Prostanoid Receptor Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    EP1 Human PTGER1 NM_000955 P34995
    Mouse Ptger1 NM_013641 P35375
    Rat Ptger1 NM_013100 P70597
    EP2 Human PTGER2 NM_000956 P43116
    Mouse Pyry2 NM_008964 Q62053
    Rat Ptger2 NM_031088 Q62928
    EP3 Human PTGER3 NM_000957 P43115
    Mouse Ptger3 NM_011196 P30557
    Rat Ptger3 NM_012704 P34980
    EP4 Human PTGER4 NM_000958 P35408
    Mouse Ptger4 NM_008965 P32240
    Rat Ptger4 NM_032076 P43114
    TP Human TBXA2R NM_201636 P21731
    Mouse Tbxa2r NM_009325 P30987
    Rat Tbxa2r NM_017054 P34978
    FP Human PTGFR NM_000959 P43088
    Mouse Ptgfr NM_008966 P43117
    Rat Ptgfr NM_013115 P43118
    IP Human PTGIR NM_000960 P43119
    Mouse Ptgir NM_008967 P43252
    Rat Ptgir NM_001077644 P43253
    DP Human PTGDR NM_000953 Q13258
    Mouse Ptgdr NM_008962 P70263
    Rat Ptgdr NM_022241 O35932

    Pathway of Prostanoid Production

    Pathway of Prostanoid Production

    Prostanoid Receptor Pharmacological Data

    Receptor Subtype EP1 EP2 EP3 EP4
    Transduction Mechanism Gq → ↑ PI hydrolysis/Ca2+ Gs → ↑ cAMP Various (splice variants), mainly ↓ cAMP Gs → ↑ cAMP
    Agonist Potencies PGE2 > PGF2, PGI2 > PGD2, TXA2 PGE2 > PGF2, PGI2 > PGD2, TXA2 PGE2 > PGF2, PGI2 > PGD2, TXA2 PGE2 > PGF2, PGI2 > PGD2, TXA2
    Receptor Distribution Kidney, lung (mouse) Lung, placenta (human), uterus, lung, ileum, liver, thymus, spleen (mouse) Kidney, uterus, stomach, brain, thymus, lung, spleen (mouse), kidney, pancreas, uterus, heart, liver, testis, ovary (human) Ileum, thymus, spleen, lung, heart, stomach, uterus (mouse)
    Tissue Functions GI contraction, tracheal contraction (guinea-pig), gastric fundus contraction Bronchodilatation (guinea-pig, cat), myometrial inhibition (human,baboon), vasodepression (cat, guinea-pig) Inhibition of gastric acid secretion (human, dog, rat), myometrial stimulation (human, cat,rat, hamster) Vasodilatation (dog), bronchodilatation (rat)

    Receptor Subtype DP FP IP TP
    Transduction Mechanism Gs → ↑ cAMP Gq → ↑ PI hydrolysis/Ca2+ Gs → ↑ cAMP
    ↑ PI hydrolysis/Ca2+
    Gq → ↑ PI hydrolysis/Ca2+
    Agonist Potencies PGD2 >> PGE2 > PGF2 > PGI2, TXA2 PGF2 > PGD2 > PGE2 > PGI2, TXA2 PGI2 >> PGD2 ,PGE2, PGF2 > TXA2 TXA2 = PGH2 >> PGD2, PGE2, PGF2, PGI2
    Receptor Distribution Ileum, lung, stomach, uterus (mouse) Corpus luteum, kidney, lung, heart, stomach (mouse), overy, small intestine, prostate, spleen, testis (human) Aorta, lung, heart, kidney (human), thymus, spleen (mouse), NTS, dorsal horn (rat) Thymus, spleen, lung, kidney, heart, uterus (mouse)
    Tissue Functions Inhibition of platelet aggregation Luteolysis Vasodepression, inhibition of platelet aggregation Vaso- and bronchoconstriction, platelet aggregation, myometrial stimulation

    References

    IUPHAR Compendium of receptor characterization and classification. (2000) 2nd Edition. IUPHAR Media. Breyer et al (2001) Prostanoid receptors: subtypes and signaling. Ann.Rev.Pharmacol.Toxicol. 41 661.