Fig. 2
From: The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures
Differential roles for S1PR1 and S1PR3 in pERK signalling in mouse and human astrocytes. Astrocytes were serum starved for 4 h before all treatments. All treatment with agonists were for 10 min and pretreatment with antagonists were at 1 μM for 1 h. Ai AUY954 (S1PR1 agonist, 1 μM), but not CYM5541 (S1PR3 agonist, 1 μM) or UC-42-WP04 (S1PR5 agonist, 1 μM) induced pERK signalling in mouse astrocytes. Bi Similar treatments with AUY954 or CYM5541, but not UC-42-WP04, induced pERK signalling in human astrocytes. Pre-treatment with NIBR-0213 (S1PR1 antagonist) fully blocked BAF312 (100 nM)-induced pERK effects in Aii and Aiii mouse and Bii and Biii human astrocytes. Pre-treatment with TY52156 (S1PR3 antagonist) showed no effect on pFTY720-mediated increase of pERK in Aiii mouse astrocytes, while Biii partially attenuating pFTY720 (100 nM)-mediated effects in human astrocytes. Data presented as ±SEM (n = 3–6), one-way ANOVA and Newman-Keuls multiple comparison post-test compared to non-treated control, *p < 0.05, **p < 0.01, ***p < 0.001, #p < 0.05, ##p < 0.001 compared to FTY720. R1 S1PR1, R3 S1PR3, R5 S1PR5, pan S1PR pan agonist, R1 Ant S1PR1 antagonist, R3 Ant S1PR3 antagonist