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Small-chain fatty acid activates astrocytic odorant receptor Olfr920

Cho, TaeHo, Lee, ChaeEun, Lee, NaHye, Hong, Yu Ri, Koo, JaeHyung
Biochemical and biophysical research communications 2019 v.510 no.3 pp. 383-387
astrocytes, brain, cyclic AMP, isobutyric acid, ligands, luciferase, odorant receptors, protein synthesis, tissues
Odorant receptors are the largest subfamily of G protein-coupled receptors and were recently suggested to play critical roles in nonolfactory tissues. However, the expression and function of odorant receptors in astrocytes, the most abundant cells in the brain, are not well known. We demonstrate that Olfr920 is highly expressed and propose that it functions as a short-chain fatty acid sensor in primary cortical astrocytes. The short-chain fatty acid isobutyric acid (IBA) was identified via a luciferase assay as an Olfr920 ligand. We show that IBA activates the Gs protein-adenylyl cyclase-cAMP pathway via Olfr920 in primary cortical astrocytes by using cAMP and knockdown analyses. In addition, IBA reduces lipopolysaccharide-induced glial fibrillary acidic protein expression in reactive astrocytes. These results suggest that astrocytic Olfr920 is a potential novel target for increased reactive astrocytes.