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. 2021 Jul 28;11:15308. doi: 10.1038/s41598-021-94052-4

Figure 4.

Figure 4

Effect of S1P receptor agonists and antagonists on PAR-mediated aggregation. Washed human platelets (2 × 108/mL) were treated with vehicle (0.2% methanol) or S1PR agonists for 5 min. Platelet aggregation were induced by subthreshold (0.6–1.0 μM) or maximal (1.5–2.0 μM) concentrations of PAR1-AP and recorded for 5 min. (a–e) (i) Representative traces of platelet aggregation induced by subthreshold PAR1-AP in the absence or presence of the (a) S1PR1 agonist SEW2871, (b) S1PR2 agonist CYM5520, (c) S1PR3 agonist CYM5541, (d) S1PR4 agonist CYM50260 or (e) S1PR5 agonist A971432. (ii) Bar graph of quantified percentage maximum aggregation induced by PAR1-AP alone or in presence of S1P receptor agonists. AU: arbitrary unit. Data are plotted as mean ± standard error of the mean. Statistical analysis: Student’s paired t-test. NS: no statistical significance; **P < 0.01, ***P < 0.001, ****P < 0.0001. (a–d) (iii) Representative traces of PAR1-AP induced platelet aggregation in the absence or presence of (a) S1PR1 antagonist Ex26, (b) S1PR2 antagonist JTE-013, (c) S1PR3 antagonist TY52156 and (d) S1PR4 antagonist CYM50358 hydrochloride. (iv) Bar graph of quantified percentage maximum aggregation induced by PAR1-AP alone or in presence of S1P receptor antagonists. AU: arbitrary unit. Data are plotted as mean ± standard error of the mean. Statistical analysis: Student’s paired t-test. NS: no statistical significance; **P < 0.01, ****P < 0.0001.