GPR75 is currently classified as an orphan GPCR and several studies are underway to identify its ligand. In one study, the chemokine CCL5 (RANTES) has been shown to stimulate calcium mobilization and inositol triphosphate formation in GPR75-transfected cells.
Recently, 20-hydroxyeicosatetraenoic acid (20-HETE), a bioactive eicosanoid formed by ω-hydroxylation of arachidonic acid has been shown to mediate its prohypertensive effects on the vasculature through activation of GPR75 (Gq) signalling. This study by Dr. Schwartzman’s laboratory at New York Medical college, one of the pioneers in study of 20-HETE biology, has opened new insights into the field of GPR75 pharmacology.
^Tarttelin EE, Kirschner LS, Bellingham J, Baffi J, Taymans SE, Gregory-Evans K, Csaky K, Stratakis CA, Gregory-Evans CY (June 1999). “Cloning and characterization of a novel orphan G-protein-coupled receptor localized to human chromosome 2p16”. Biochemical and Biophysical Research Communications. 260 (1): 174–80. doi:10.1006/bbrc.1999.0753. PMID10381362.