Astrocytes are type of neuroglial cells in the central nervous system, which are positioned between capillaries and neurons. They can uptake glucose from blood through glucose transporters. Glucose can be stored in astrocytes in glycogen and during intense brain activity metabolised to lactate in the process of aerobic glycolysis. Neurons can uptake lactate via lactate transporters and use it as an energy source. Astrocytes express G-protein coupled receptors (GPCR) on their surface, which upon activation trigger intracellular Ca2+ and cAMP signaling pathways. The latter regulate glucose metabolism in astrocytes. GPR120/FFAR4 and GPR40/FFAR1 are GPCRs, activated by long chain free fatty acids. Their role in brain is poorly understood. Our aim was to study the effect of selective agonists of GPR120/FFAR4, TUG-891, and GPR40/FFAR1, TAK-875, on intracellular signalling pathways of Ca2+ and cAMP and glucose metabolism in astrocytes. Using fluorescent Ca2+-indicator Fluo-4 AM and FRET-nanosensors in combination with real time confocal microscopy, we monitored changes in intracellular level of Ca2+, cAMP, glucose and lactate in cultured rat cortical astrocytes upon stimulation with agonists TUG-891 or TAK-875. Stimulation with 10 μM TUG-891 had no effect on intracellular Ca2+ concentration, but caused a rise in concentration of cAMP and lactate, which indicates coupling of GPR120/FFAR4 with Gs-protein and activation of cAMP signaling pathway and aerobic glycolysis. Stimulation with 10 μM TUG-891 or TAK-875 had no effect on intracellular free glucose level. We assume that agonists do not affect uptake of extracellular glucose, which depends on intracellular Ca2+-concentration, on which agonists had no effect.
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