RT Journal Article SR Electronic T1 International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors JF Pharmacological Reviews JO Pharmacol Rev FD American Society for Pharmacology and Experimental Therapeutics SP 500 OP 543 DO 10.1124/pr.111.005223 VO 65 IS 1 A1 Andreas Klos A1 Elisabeth Wende A1 Kathryn J. Wareham A1 Peter N. Monk YR 2013 UL http://pharmrev.aspetjournals.org/content/65/1/500.abstract AB The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small (74–77 amino acid) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types. These fragments, C5a, C4a, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration. Their primary function, however, is in inflammation, so they are important targets for the development of anti-inflammatory therapies. Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation. In humans, there is a single receptor for C3a (C3a receptor), no known receptor for C4a, and two receptors for C5a (C5a1 receptor and C5a2 receptor). The most recently characterized receptor, the C5a2 receptor (previously known as C5L2 or GPR77), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this. Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology.