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- W2941312336 abstract "Sphingosine-1-phosphate (S1P) plays important roles as a signaling lipid in a variety of physiological and pathophysiological processes. S1P signals via a family of G-protein-coupled receptors (GPCRs) (S1P1–5) and intracellular targets. Here, we report on photoswitchable analogs of S1P and its precursor sphingosine, respectively termed PhotoS1P and PhotoSph. PhotoS1P enables optical control of S1P1–3, shown through electrophysiology and Ca2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P3-dependent pain hypersensitivity in mice. The hypersensitivity induced by PhotoS1P is comparable to that induced by S1P. PhotoS1P is uniquely suited for the study of S1P biology in cultured cells and in vivo because it exhibits prolonged metabolic stability compared to the rapidly metabolized S1P. Using lipid mass spectrometry analysis, we constructed a metabolic map of PhotoS1P and PhotoSph. The formation of these photoswitchable lipids was found to be light dependent, providing a novel approach to optically probe sphingolipid biology. A photoswitchable analog of spingosine-1-phosphate (S1P) that allows for modulation of the action of this bioactive lipid exhibits prolonged metabolic stability compared to S1P, activates S1P receptors in cells and mediates nociception in mice." @default.
- W2941312336 created "2019-05-03" @default.
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- W2941312336 date "2019-04-29" @default.
- W2941312336 modified "2023-10-06" @default.
- W2941312336 title "Optical control of sphingosine-1-phosphate formation and function" @default.
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- W2941312336 doi "https://doi.org/10.1038/s41589-019-0269-7" @default.
- W2941312336 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7428055" @default.
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