The GPR32 was initially identified and defined by
molecular cloning in 1998 as coding for an
orphan receptor, i.e. a protein with an amino acid sequence similar to known receptors but having no known
ligand(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 the
chemotactic factor receptor family, i.e. 39% identity with
Formyl peptide receptor 1, which is a receptor for
N-Formylmethionine-leucyl-phenylalanine and related N-formyl peptide chemotactic factors, and 35% identity with
Formyl peptide receptor 2, which likewise is also a receptor for N-formyl peptides but also a receptor for certain
lipoxins which are
arachidonic acid metabolites belonging to a set of
specialized proresolving mediators that act to resolve or inhibit inflammatory reactions. GPR32 mapped to chromosomal 19, region q13.3.[4] There are no mouse or other
orthologs of GPR32.[5]
Receptor
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 blood
neutrophils, certain types of blood
lymphocytes (i.e. activated
CD8+ cells,
CD4+ T cells, and
T helper 17 cells), tissue
macrophages, small airway
epithelial cells, and adipose tissue.[5][6][7] When expressed in
Chinese hamster ovary cells, GPR32 inhibits the
Cyclic 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 of
resolvins (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 (see
resolvin mechanisms of action).[9][10][11] RvDs are members of the
specialized proresolving mediators (SPM) class of
polyunsaturated fatty acid metabolites. RVDs are metabolites of the
omega-3 fatty acid,
docosahexaenoic acid (DHA), and, along with other SRMs contribute to the inhibition and resolution of a diverse range of
inflammation 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.
Further reading
Marchese A, Nguyen T, Malik P, Xu S, Cheng R, Xie Z, Heng HH, George SR, Kolakowski LF, O'Dowd BF (June 1998). "Cloning genes encoding receptors related to chemoattractant receptors". Genomics. 50 (2): 281–6.
doi:
10.1006/geno.1998.5297.
PMID9653656.