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
| Autor: | Shelagh Wilson, Richard L.M. Faull, Philip G. Szekeres, Jeannette M. Watson, Paul R. Murdock, Henry J. Waldvogel, Darren J. Moore, Katie Freeman, Piers C. Emson |
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| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty P2Y receptor Neuroimmunomodulation G protein GTP-Binding Protein alpha Subunits Gi-Go Biology Uridine Diphosphate Cell Line Receptors G-Protein-Coupled Cellular and Molecular Neuroscience Immune system Internal medicine Gene expression Leukocytes medicine Animals Humans RNA Messenger Receptors Immunologic Receptor Molecular Biology Receptors Purinergic P2 Brain Human brain Immunohistochemistry Rats Up-Regulation Cell biology Protein Subunits Glucose medicine.anatomical_structure Endocrinology Gene Expression Regulation Cell culture Astrocytes Receptors Purinergic P2Y GTP-Binding Protein alpha Subunits Gq-G11 Neuroglia |
| Zdroj: | Molecular Brain Research. 118:10-23 |
| ISSN: | 0169-328X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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