Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Mar;16(1):5-46.
doi: 10.1007/s12079-021-00630-6. Epub 2021 Jun 26.

A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action

Roger G Biringer  1
Affiliations
Review

A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action

Roger G Biringer. J Cell Commun Signal. 2022 Mar.

Abstract

Eicosanoid signaling controls a wide range of biological processes from blood pressure homeostasis to inflammation and resolution thereof to the perception of pain and to cell survival itself. Disruption of normal eicosanoid signaling is implicated in numerous disease states. Eicosanoid signaling is facilitated by G-protein-coupled, eicosanoid-specific receptors and the array of associated G-proteins. This review focuses on the expression, characterization, regulation, and mechanism of action of non-prostanoid, eicosanoid receptors.

Keywords: Eicosanoid; G-protein; Protectin; Receptor; Resolvin; Signaling.

PubMed Disclaimer

Conflict of interest statement

The author declares that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Metabolic pathways for non-prostanoid eicosanoids derived from arachidonic acid and their receptors. Gene designations are given for the participating enzymes (rounded boxes), accepted acronyms are given for metabolites (ovals) and accepted receptor acronyms in grey squares. Black arrows indicate enzymatic reactions and grey arrows indicate receptor binding. Enzymes are as follows: 12/15-LOX, 12/15-lipoxygenase; 5-HEDH, 5-hydroxyeicosanoid dehydrogenase; ALOX12, Arachidonate 12(S)-lipoxygenase; ALOX12B, arachidonate 12(R)-lipoxygenase; LTC4S, leukotriene C4 synthase; ALOX15, arachidonate 15-lipoxygenase-1; ALOX15B, arachidonate 15-lipoxygenase-2; ALOX5, Arachidonate 5-lipoxygenase; ALOXE3, arachidonate lipoxygenase 3; CYP2C, cytochrome P450 C2; CYP4F2, cytochrome P450 4F; CYP2J, cytochrome P450 J2; DPEP, dipeptidase; GPX, glutathione peroxidase; LTA4H, Leukotriene A-4 hydrolase; LTC4S, leukotriene C4 synthase; PTGS1, Prostaglandin G/H Synthase 1; PTGS2, Prostaglandin G/H Synthase 2; PTGS2/aspirin, PTGS2 acetylated by aspirin; sEH, soluble epoxide hydrolase; TBXAS1, Thromboxane A Synthase 1. Abbreviations for metabolites: 8,9-EET, 8,9-EET, 8,9-epoxy-5Z,11Z,14Z-eicosatrienoic acid; 11,12-EET, 11,12-epoxy-5Z,8Z,14Z-eicosatrienoic acid; 14,15-EET, 14,15-epoxy-5Z,8Z,11Z-eicosatrienoic acid; 11(R),12(R)-HXA3, 11(R),12(R)-Hepoxilin A3; 11(S),12(S)-HXA3, 11(S),12(S)-Hepoxilin A3; 11(S),12(S)-HXB3, 11(S),12(S)-Hepoxilin B3; 11(R),12(R)-TrXA3, 11(R),12(R)-trioxilin A3;11(S),12(S)-TrXA3, 11(S),12(S)-trioxilin A3; 11(S),11(S)-TrXB3, 11(S),12(S)-trioxilin B3; 5-oxo-ETE, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid; 12(S)-HETE, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid; 12(S)-HPETE, 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid; 5(S)-HETE, 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 5(S)-HPETE, 5S-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 15(S)-HPETE, 15S-hydroperoxy-5Z,8Z,11Z,13E- eicosatetraenoic acid; 15(S)-HPETE, 15S-hydroperoxy-5Z,8Z,11Z,13E- eicosatetraenoic acid; 15(R)-HETE, 15R-hydroxy-5Z,8Z,11Z,13E- eicosatetraenoic acid;12(R)-HPETE, 12R-hydroperoxy-5Z,8Z,10E,12R,14Z- eicosatetraenoic acid; 12(R)-HETE, 12R-hydroxy-5Z,8Z,10E,12R,14Z- eicosatetraenoic acid; 12-KETE, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid;12-HHT, 12-Hydroxy-5,8,10-heptadecatrienoic acid; AA, arachidonic acid; 20-HETE, 20-Hydroxyeicosatetraenoic acid; 5(S),6(S)-Ep-15(R)-HETE, 5S,6S-epoxy-15(R)-hydroxy-7E,9E,11Z,13E-eicosatetraenoic acid; 5(S),6(S)-Ep-15(S)-HETE, 5S,6S-epoxy-15(S)-hydroxy-7E,9E,11Z,13E-eicosatetraenoic acid; 15-epi-LXA4, 15-epi-lipoxin A4; 15-epi-LXB4, 15-epi-lipoxin B4; LTA4, leukotriene A4; LTB4, leukotriene B4; LTC4, leukotriene C4; LTD4, leukotriene D4; LTE4, leukotriene E4; LXA4, lipoxin A4; LXB4, lipoxin B4; EXA4, eoxin A4; EXC4, eoxin C4; EXD4, eoxin D4; EXE4, eoxin E4; PGH2, prostaglandin H2. Receptors are as follows: CYSLTR1, cysteinyl leukotriene receptor 1; CYSLTR2, cysteinyl leukotriene receptor 2; FFAR1, free fatty acid receptor 1; FPR2/ALX, N-formyl peptide receptor 2; GPR17, uracil nucleotide/cysteinyl leukotriene receptor; GPR31, 12S-hydroxy-5,8,10,14-eicosatetraenoic acid receptor; GPR32, Probable G-protein coupled receptor 32; GPR75, Probable G-protein coupled receptor 75; LTB4R, Leukotriene B4 receptor 1; LTB4R2, leukotriene B4 receptor 2; OXER1, oxoeicosanoid receptor 1; OXGR1 (GPR99), 2-oxoglutarate receptor 1; P2Y12, P2Y purinoceptor 12; TP, Thromboxane A2 receptor (TBXAR2); TRPV1, Transient receptor potential cation channel subfamily V member 1
Fig. 2
Fig. 2
Metabolic pathways for non-prostanoid eicosanoids derived from eicosapentaenoic acid (EPA) and dicosahexaenoic acid (DHA). Gene designations are given for the participating enzymes (rounded boxes), accepted acronyms are given for metabolites (ovals) and accepted receptor acronyms in grey squares. Black arrows indicate enzymatic reactions and grey arrows indicate receptor binding. Enzymes are as follows: ALOX, unspecified lipoxygenase; ALOX15, arachidonate 15-lipoxygenase-1; ALOX5, Arachidonate 5-lipoxygenase; GPX, glutathione peroxidase; Hyd, unspecified hydrolase; P450, unspecified P450 enzyme; PTGS2/aspirin, PTGS2 acetylated by aspirin. Abbreviations for metabolites: 11(R),12(R)-HXA3, 11(R),12(R)-Hepoxilin A3; 11(R),12(R)-TrXA3, 11(R),12(R)-trioxilin A3; 11(R),12(S)-TrXB3, 11R,12(S)-trioxilin B3; 11(S),12(S)-HXA3, 11(S),12(S)-Hepoxilin A3; 11(S),12(S)-HXB3, 11(S),12(S)-Hepoxilin B3; 11(S),12(S)-TrXA3, 11(S),12(S)-trioxilin A3; 12(S)-HETE, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid; 12(S)-HPETE, 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid; 15(R)-HETE, 15R-hydroxy-5Z,8Z,11Z,13E- eicosatetraenoic acid; 15(S)-HPETE, 15S-hydroperoxy-5Z,8Z,11Z,13E- eicosatetraenoic acid; 15(S)-HPETE, 15S-hydro peroxy-5Z,8Z,11Z,13E- eicosatetraenoic acid; 17(R)-HDHA, 17R-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid; 17(R)-HPDHA, 17R-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid; 17(R)-RvD1, 17(R)-resolvin D1; 17(R)-RvE2, 17(R)-resolvin E2; 17(S)-HDHA, 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid; 17(S)-HPDHA, 17S-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid; 17(S)-HPDHA, 17S-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid; 17(S)-RvD1, 17(S)-resolvin D1; 17(S)-RvD2, 17(S)-resolvin D2; 17(S)-RvE2, 17(S)-resolvin E2; 18(R)-HEPE, 18R-hydroxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid; 18(R)-HPEPE, 18R-hydroperoxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid; 18(R)-RvE2, 18(R)-resolvin E2; 18(R)-RvE2, 18(R)-resolvin E2; 18(S)-HEPE, 18S-hydroxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid; 18(S)-HPEPE, 18S-hydroperoxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid; 18(S)-RvE1, 18(S)-resolvin E1;18(S)-RvE2, 18(S)-resolvin E2; 5(S),6(S)-Ep-18(R)-HEPE, 5S,6S-epoxy,18R-hydroxy-7E,9E,11Z,14Z,16E-eicosapentaenoic acid; 5(S),6(S)-Ep-18(S)-HEPE, 5S,6S-epoxy,18S-hydroxy-7E,9E,11Z,14Z,16E-eicosapentaenoic acid; 5(S)-Hp-18(R)-HEPE, 5S-hydroperoxy-18R-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate; 5(S)-Hp-18(S)-HEPE, 5S-hydroperoxy-18S-hydroxy-(6E,8Z,11Z,14Z,16E)-icosapentaenoate; 5-oxo-ETE, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid; 5S-HETE, 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 5(S)-HPETE, 5S-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 7(S),8(S)-Ep-17(R)-HDHA, 7S,8S-epoxy-17R-hydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic; 7(S),8(S)-Ep-17(S)-HDHA, 7S,8S-epoxy-17S-hydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic; DHA, docosahexaenoic acid; EPA, Eicosapentaenoic acid. Receptors are as follows: CMKLR1, Chemokine-Like Receptor 1; FPR2/ALX, N-formyl peptide receptor 2; GPR18, N-Arachidondyl Glycine Receptor; GPR32, G-Protein Receptor 32
See this image and copyright information in PMC

References

    1. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev. 2006;58:281–341. doi: 10.1124/pr.58.3.3. - DOI - PMC - PubMed
    1. Adolfsson JL, Ohd JF, Sjölander A. Leukotriene D4-induced activation and translocation of the G-protein alpha i3-subunit in human epithelial cells. Biochem Biophys Res Commun. 1996;226:413–419. doi: 10.1006/bbrc.1996.1370. - DOI - PubMed
    1. Aizawa F, Nishinaka T, Yamashita T, Nakamoto K, Kurihara T, Hirasawa A, Kasuya F, Miyata A, Tokuyama S. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior. J Pharmacol Sci. 2016;132:249–254. doi: 10.1016/j.jphs.2016.09.007. - DOI - PubMed
    1. Andrew W, Martino B, Stefan B, Gabriel S, Gerardo T, Rafal GH, Florian T, de Beer TAP, Christine R, Lorenza B, Rosalba L, Torsten S. SWISS-MODEL homology modelling of protein structures and complexes. Nucleic Acids Research. 2018;46(1):296–303. - PMC - PubMed
    1. Aratake Y, Okuno T, Matsunobu T, Saeki K, Takayanagi R, Furuya S, Yokomizo T. Helix 8 of leukotriene B4 receptor 1 inhibits ligand-induced internalization. FASEB J. 2012;26:4068–4078. doi: 10.1096/fj.12-212050. - DOI - PubMed

LinkOut - more resources