C3a receptor explained

The C3a receptor also known as complement component 3a receptor 1 (C3AR1) is a G protein-coupled receptor protein involved in the complement system.^{[1] [2]}

The receptor binds to complement component C3a, although there is limited evidence that this receptor also binds C4a in lesser mammals. This has yet to be proven true in humans.^[3] C3a receptor modulates immunity,^[4] arthritis, diet-induced obesity^[5] and cancers.^[6]

Agonists and antagonists

Potent and selective agonists^[7] and antagonists^[8] for C3aR have been discovered.

Further reading

• Sim RB, Laich A . Serine proteases of the complement system . Biochemical Society Transactions . 28 . 5 . 545–50 . October 2000 . 11044372 . 10.1042/bst0280545.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Roglic A, Prossnitz ER, Cavanagh SL, Pan Z, Zou A, Ye RD . cDNA cloning of a novel G protein-coupled receptor with a large extracellular loop structure . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1305 . 1–2 . 39–43 . February 1996 . 8605247 . 10.1016/0167-4781(95)00209-x .
• Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C . Molecular cloning and characterization of the human anaphylatoxin C3a receptor . The Journal of Biological Chemistry . 271 . 34 . 20231–4 . August 1996 . 8702752 . 10.1074/jbc.271.34.20231 . free .
• Crass T, Raffetseder U, Martin U, Grove M, Klos A, Köhl J, Bautsch W . Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cells . European Journal of Immunology . 26 . 8 . 1944–50 . August 1996 . 8765043 . 10.1002/eji.1830260840 . 24586216 .
• Ames RS, Nuthulaganti P, Kumar C . In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins . FEBS Letters . 395 . 2–3 . 157–9 . October 1996 . 8898085 . 10.1016/0014-5793(96)01018-6 . 39187651 . free .
• Martin U, Bock D, Arseniev L, Tornetta MA, Ames RS, Bautsch W, Köhl J, Ganser A, Klos A . The human C3a receptor is expressed on neutrophils and monocytes, but not on B or T lymphocytes . The Journal of Experimental Medicine . 186 . 2 . 199–207 . July 1997 . 9221749 . 2198980 . 10.1084/jem.186.2.199 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Hollmann TJ, Haviland DL, Kildsgaard J, Watts K, Wetsel RA . Cloning, expression, sequence determination, and chromosome localization of the mouse complement C3a anaphylatoxin receptor gene . Molecular Immunology . 35 . 3 . 137–48 . February 1998 . 9694514 . 10.1016/S0161-5890(98)00021-2 .
• Lienenklaus S, Ames RS, Tornetta MA, Sarau HM, Foley JJ, Crass T, Sohns B, Raffetseder U, Grove M, Hölzer A, Klos A, Köhl J, Bautsch W . Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor . Journal of Immunology . 161 . 5 . 2089–93 . September 1998 . 10.4049/jimmunol.161.5.2089 . 9725198 . 29247962 . free .
• Davoust N, Jones J, Stahel PF, Ames RS, Barnum SR . Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells . Glia . 26 . 3 . 201–11 . May 1999 . 10340761 . 10.1002/(SICI)1098-1136(199905)26:3<201::AID-GLIA2>3.0.CO;2-M . 38751182 .
• Settmacher B, Bock D, Saad H, Gärtner S, Rheinheimer C, Köhl J, Bautsch W, Klos A . Modulation of C3a activity: internalization of the human C3a receptor and its inhibition by C5a . Journal of Immunology . 162 . 12 . 7409–16 . June 1999 . 10.4049/jimmunol.162.12.7409 . 10358194 . 9269285 . free .
• Feild JA, Foley JJ, Testa TT, Nuthulaganti P, Ellis C, Sarau HM, Ames RS . Cloning and characterization of a rabbit ortholog of human Galpha16 and mouse G(alpha)15 . FEBS Letters . 460 . 1 . 53–6 . October 1999 . 10571060 . 10.1016/S0014-5793(99)01317-4 . 86483726 .
• Petering H, Köhl J, Weyergraf A, Dulkys Y, Kimmig D, Smolarski R, Kapp A, Elsner J . Characterization of synthetic C3a analog peptides on human eosinophils in comparison to the native complement component C3a . Journal of Immunology . 164 . 7 . 3783–9 . April 2000 . 10725738 . 10.4049/jimmunol.164.7.3783 . free .
• Drouin SM, Kildsgaard J, Haviland J, Zabner J, Jia HP, McCray PB, Tack BF, Wetsel RA . Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma . Journal of Immunology . 166 . 3 . 2025–32 . February 2001 . 11160252 . 10.4049/jimmunol.166.3.2025 . free .
• Ames RS, Lee D, Foley JJ, Jurewicz AJ, Tornetta MA, Bautsch W, Settmacher B, Klos A, Erhard KF, Cousins RD, Sulpizio AC, Hieble JP, McCafferty G, Ward KW, Adams JL, Bondinell WE, Underwood DC, Osborn RR, Badger AM, Sarau HM . Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models . Journal of Immunology . 166 . 10 . 6341–8 . May 2001 . 11342658 . 10.4049/jimmunol.166.10.6341 . free .
• Kirchhoff K, Weinmann O, Zwirner J, Begemann G, Götze O, Kapp A, Werfel T . Detection of anaphylatoxin receptors on CD83+ dendritic cells derived from human skin . Immunology . 103 . 2 . 210–7 . June 2001 . 11412308 . 1783227 . 10.1046/j.1365-2567.2001.01197.x .
• Reca R, Mastellos D, Majka M, Marquez L, Ratajczak J, Franchini S, Glodek A, Honczarenko M, Spruce LA, Janowska-Wieczorek A, Lambris JD, Ratajczak MZ . Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1 . Blood . 101 . 10 . 3784–93 . May 2003 . 12511407 . 10.1182/blood-2002-10-3233 . 12692309 . free .

External links

• Web site: Anaphylatoxin Receptors: C3a . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-10-25 . 2016-03-03 . https://web.archive.org/web/20160303171826/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2973 . dead .

Notes and References

1. Roglic A, Prossnitz ER, Cavanagh SL, Pan Z, Zou A, Ye RD . cDNA cloning of a novel G protein-coupled receptor with a large extracellular loop structure . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1305 . 1–2 . 39–43 . February 1996 . 8605247 . 10.1016/0167-4781(95)00209-x .
2. Ali H, Panettieri RA . Anaphylatoxin C3a receptors in asthma . Respiratory Research . 6 . 19 . February 2005 . 1 . 15723703 . 551592 . 10.1186/1465-9921-6-19 . free .
3. Klos A, Wende E, Wareham KJ, Monk PN . International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors . Pharmacological Reviews . 65 . 1 . 500–43 . January 2013 . 23383423 . 10.1124/pr.111.005223 . free .
4. Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS . Immune cell-derived C3a and C5a costimulate human T cell alloimmunity . American Journal of Transplantation . 13 . 10 . 2530–9 . October 2013 . 24033923 . 3809075 . 10.1111/ajt.12405 .
5. Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP . C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling . FASEB Journal . 27 . 2 . 822–31 . February 2013 . 23118029 . 10.1096/fj.12-220582 . free . 25562647 .
6. Sayegh ET, Bloch O, Parsa AT . Complement anaphylatoxins as immune regulators in cancer . Cancer Medicine . 3 . 4 . 747–58 . August 2014 . 24711204 . 4303144 . 10.1002/cam4.241 .
7. Reid RC, Yau MK, Singh R, Hamidon JK, Reed AN, Chu P, Suen JY, Stoermer MJ, Blakeney JS, Lim J, Faber JM, Fairlie DP . Downsizing a human inflammatory protein to a small molecule with equal potency and functionality . Nature Communications . 4 . 2802 . 2013 . 24257095 . 10.1038/ncomms3802 . 2013NatCo...4.2802R . free .
8. Reid RC, Yau MK, Singh R, Lim J, Fairlie DP . Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides . Journal of the American Chemical Society . 136 . 34 . 11914–7 . August 2014 . 25102224 . 10.1021/ja506518t .