GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function

• Published in: Brain research. Molecular brain research. Vol. 118; no. 1-2; pp. 10 - 23
• Main Authors: MOORE, Darren J, MURDOCK, Paul R, WATSON, Jeannette M, FAULL, Richard L. M, WALDVOGEL, Henry J, SZEKERES, Philip G, WILSON, Shelagh, FREEMAN, Katie B, EMSON, Piers C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 21.10.2003
• Subjects: Animals; Astrocytes - immunology; Astrocytes - metabolism; Biological and medical sciences; Brain - immunology; Brain - metabolism; Cell Line; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Glucose - immunology; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Humans; Immunohistochemistry; Leukocytes - immunology; Leukocytes - metabolism; Lipopolysaccharides - immunology; Male; Miscellaneous; Molecular and cellular biology; Neuroimmunomodulation - immunology; Protein Subunits - genetics; Protein Subunits - metabolism; Rats; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - immunology; Receptors, G-Protein-Coupled - metabolism; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2 - immunology; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2Y; RNA, Messenger - metabolism; Up-Regulation - immunology; Uridine Diphosphate - immunology; Glial cell; P2Y14; Neuroglia; Central nervous system; Extracellular nucleotide; Glial cells; Gene expression; Encephalon; Immunologic challenge; P2Y purinergic receptor; P2Y receptor; UDP-glucose; GPR105; Immunocyte; G protein; Biological receptor
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/s0169-328x(03)00330-9

We have recently shown that UDP-glucose, and some related UDP-sugars, are potent agonists of the novel G protein-coupled receptor GPR105 (recently re-named P2Y(14)). GPR105 is widely expressed throughout many brain regions and peripheral tissues of human and rodents, and couples to a pertussis toxin-sensitive G protein. To further characterise the role of GPR105, we demonstrate by immunohistochemistry with receptor-specific antiserum that GPR105 protein is widely distributed throughout the post mortem human brain where it is localised to glial cells, and specifically co-localises with astrocytes. Using quantitative RT-PCR we also show that GPR105 mRNA exhibits a restricted expression profile in an array of human cell lines and primary cells, with prominent expression detected in immune cells including neutrophils, lymphocytes, and megakaryocytic cells. To investigate the G protein selectivity of GPR105, we used chimeric Galpha subunits (Galpha(qi5), Galpha(qo5), and Galpha(qs5)) and an intracellular Ca(2+) mobilisation assay to demonstrate that GPR105 couples to Galpha subunits of the G(i/o) family but not to G(s) family proteins or to endogenous G(q/11) proteins in HEK-293 cells. Finally, we show that expression of GPR105 mRNA in the rat brain is up-regulated by immunologic challenge with lipopolysaccharide. Based on these observations, we propose that G(i/o)-coupled GPR105 might play an important role in peripheral and neuroimmune function in response to extracellular UDP-sugars.