TheGPR32 was initially identified and defined bymolecular cloning in 1998 as coding for anorphan receptor, i.e. a protein with an amino acid sequence similar to known receptors but having no knownligand(s) to which it responds and no known function. The projected amino acid sequence of GPR32, however, shared 35-39% amino acid identity with certain members of thechemotactic factor receptor family, i.e. 39% identity withFormyl peptide receptor 1, which is a receptor forN-Formylmethionine-leucyl-phenylalanine and related N-formyl peptide chemotactic factors, and 35% identity withFormyl peptide receptor 2, which likewise is also a receptor for N-formyl peptides but also a receptor for certainlipoxins which arearachidonic acid metabolites belonging to a set ofspecialized proresolving mediators that act to resolve or inhibit inflammatory reactions. GPR32 mapped to chromosomal 19, region q13.3.[4] There are no mouse or otherorthologs of GPR32.[5]
The GPR32 protein is a G protein coupled receptor although the specific G protein subtypes which it activates has not yet been reported. GPR32 is expressed in human bloodneutrophils, certain types of bloodlymphocytes (i.e. activatedCD8+ cells,CD4+ T cells, andT helper 17 cells), tissuemacrophages, small airwayepithelial cells, and adipose tissue.[5][6][7] When expressed inChinese hamster ovary cells, GPR32 inhibits theCyclic adenosine monophosphate signaling pathway under both baseline and forskolin-stimulated conditions indicating that it is a member of the class of orphan G protein coupled receptors that possesses constitutive signaling activity.[8]
At least 6 members of the D series ofresolvins (RvDs) viz., RvD1, RvD2m AT-RVD1, RvD3, AT-RvD3, and RvD5, activate their target cells through this receptor; these results have led to naming GPR32 the RVD1 receptor (seeresolvin mechanisms of action).[9][10][11] RvDs are members of thespecialized proresolving mediators (SPM) class ofpolyunsaturated fatty acid metabolites. RVDs are metabolites of theomega-3 fatty acid,docosahexaenoic acid (DHA), and, along with other SRMs contribute to the inhibition and resolution of a diverse range ofinflammation and inflammation-related responses as well as to the healing of these inflammatory lesions in animals and humans.[12] The metabolism of DHA to RVD's and the activation of GPR32 by these RVD's are proposed to be one mechanism by which omega-3 fatty acids may ameliorate inflammation as well as various inflammation-based and other diseases.[13]
^Headland SE, Norling LV (May 2015). "The resolution of inflammation: Principles and challenges".Seminars in Immunology.27 (3):149–60.doi:10.1016/j.smim.2015.03.014.PMID25911383.
^Calder PC (April 2015). "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance".Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.1851 (4):469–84.doi:10.1016/j.bbalip.2014.08.010.PMID25149823.
