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

Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):10-23. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Brain / immunology
  • Brain / metabolism*
  • Cell Line
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Glucose / immunology
  • Humans
  • Immunohistochemistry
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Lipopolysaccharides / immunology
  • Male
  • Neuroimmunomodulation / immunology
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA, Messenger / 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
  • Up-Regulation / immunology
  • Uridine Diphosphate / immunology


  • Lipopolysaccharides
  • P2RY14 protein, human
  • Protein Subunits
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Immunologic
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y
  • Uridine Diphosphate
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Glucose