The formylpeptide receptors (nomenclature agreed by the NC-IUPHAR Subcommittee on the formylpeptide receptor family [25]) respond to exogenous ligands such as the bacterial product fMet-Leu-Phe (fMLF) and endogenous ligands such as lipoxin A₄ (LXA₄), 15-epi-lipoxin A₄, annexin I (ANXA1, P04083) , cathepsin G (CTSG, P08311), amyloid β42, serum amyloid A and spinorphin, derived from β-haemoglobin (HBB, P68871). FPR1 also serves as a plague receptor for selective destruction of human immune cells by Y. pestis [23]. The FPR1/2 agonists 'compound 17b' and 'compound 43' have shown cardiac protective functions [10,24].

Note that the data for FPR2/ALX are also reproduced on the leukotriene receptor page.
FPR1 has been reported to be the plague receptor on host immune cells [23]. By interacting with LcrV, the needle cap protein of the type III secretion system of Y. pestis, FPR1 serves to promote translocation of virulent factors of the bacteria. The R190W mutation of FPR1 confers resistance to this function of Y. pestis. Several FPR1/2 agonists including 'compound 17b' and 'compound 43' have been shown to display cardiac protective functions in mouse models of myocardial ischemia-reperfusion injury [10,24]. Studies have been conducted to explore the mechanisms by which FPR2 mediates both inflammatory and anti-inflammatory signaling in a ligand-dependent manner. The status of FPR2 dimerization is a determining factor for ligand-specific conformational changes leading to biased signaling [4]. There is also a report on ligand concentration-dependent dual modulation of FPR2 by lipoxin A₄ for receptor-activation vs. anti-inflammatory activities [11]. Some FPR2 ligands may display allosteric modulatory effects that cause changes in FPR2 conformational states and receptor signaling [33]. The 3-D structure of FPR2 has been solved by the use of cryo-electron microscopy [34] and receptor protein crystallization [2]. The FPR2 structure reveals a large binding pocket that can accommodate several ligands of different shapes and sizes.

* Key recommended reading is highlighted with an asterisk

* Dahlgren C, Gabl M, Holdfeldt A, Winther M, Forsman H. (2016) Basic characteristics of the neutrophil receptors that recognize formylated peptides, a danger-associated molecular pattern generated by bacteria and mitochondria. Biochem Pharmacol, 114: 22-39. [PMID:27131862]

* Dorward DA, Lucas CD, Chapman GB, Haslett C, Dhaliwal K, Rossi AG. (2015) The Role of Formylated Peptides and Formyl Peptide Receptor 1 in Governing Neutrophil Function during Acute Inflammation. Am J Pathol, 185 (5): 1172-1184. [PMID:25791526]

Gavins FN. (2010) Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia-reperfusion injury?. Trends Pharmacol Sci, 31 (6): 266-76. [PMID:20483490]

* Krepel SA, Wang JM. (2019) Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors. Int J Mol Sci, 20 (14). [PMID:31336833]

Liberles SD, Horowitz LF, Kuang D, Contos JJ, Wilson KL, Siltberg-Liberles J, Liberles DA, Buck LB. (2009) Formyl peptide receptors are candidate chemosensory receptors in the vomeronasal organ. Proc Natl Acad Sci USA, 106 (24): 9842-7. [PMID:19497865]

* Perretti M, Godson C. (2020) Formyl peptide receptor type 2 agonists to kick-start resolution pharmacology. Br J Pharmacol, 177 (20): 4595-4600. [PMID:32954491]

* Yazid S, Norling LV, Flower RJ. (2012) Anti-inflammatory drugs, eicosanoids and the annexin A1/FPR2 anti-inflammatory system. Prostaglandins Other Lipid Mediat, 98 (3-4): 94-100. [PMID:22123264]

* Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN, Murphy PM. (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev, 61 (2): 119-61. [PMID:19498085]

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12. Gronert K, Martinsson-Niskanen T, Ravasi S, Chiang N, Serhan CN. (2001) Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses. Am J Pathol, 158 (1): 3-9. [PMID:11141472]

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Subcommittee members: Richard D. Ye (Chairperson) School of Life and Health Sciences The Chinese University of Hong Kong, Shenzhen Guangdong, 518172 China François Boulay Commissariat à l’Energie Atomique Institut de Recherches en Technologies et Sciences pour le Vivant Laboratoire de Biochimie et de Biophysique des Systèmses Intégrés Grenoble France Claes Dahlgren Department of Rheumatology and Inflammation Research University of Göteborg Göteborg Sweden Craig Gerard Department of Pediatrics Harvard Medical School and Children's Hospital Boston Massachusetts U.S.A Philip M. Murphy Head, Molecular Signaling Section, Laboratory of Molecular Immunology, and Chief, Laboratory of Molecular Immunology National Institute of Allergy and Infectious Diseases National Institutes of Health 9000 Rockville Pike MSC-1888 Bldg. 10, Room 11N113 Bethesda MD 20892 USA Marc Parmentier Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM) Université Libre de Bruxelles Brussels Belgium Mark Quinn Department of Microbiology and Immunology Montana State University Bozeman, MT 59717 U.S.A. Charles N. Serhan Center for Experimental Theraputics and Reperfusion Injury Brigham and Women's Hospital Hale Building for Transformative Medicine 60 Fenwood Road, Suite 3-016 Boston, MA 02115 USA Ji Ming Wang Laboratory of Molecular Immunoregulation Cancer and Inflammation Program Center for Cancer Research National Cancer Institute at Frederick Frederick Maryland USA

Other contributors: Magnus Bäck Translational Cardiology Karolinska Institutet, Department of Medicine Karolinska University Hospital M85 141 86 Stockholm Sweden Nan Chiang Center for Experimental Theraputics and Reperfusion Injury Brigham and Women's Hospital Hale Building for Transformative Medicine 60 Fenwood Road, Suite 3-016 Boston, MA 02115 USA Sven-Erik Dahlén Unit for Experimental Asthma and Allergy Research The National Institute of Environmental Medicine Karolinska Institutet S-171 77 Stockholm Sweden Jeffrey Drazen Respiratory Division Brigham and Woman's Hospital 75 Francis Street Boston, MA 02115 USA Jilly F. Evans PharmAkea 12780 El Camino Real San Diego, CA 92130 USA G. Enrico Rovati (Past contributor (deceased)) Formerly of the Laboratory of Molecular Pharmacology University of Milan Italy Takao Shimizu National Center for Global Health and Medicine Shinjyuku Tokyo 166-8655 Japan Takehiko Yokomizo Department of Biochemistry Juntendo University School of Medicine Hongo 2-1-1 Bunkyo-ku Tokyo 113-8421 Japan