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Figure 7 | Journal of Neuroinflammation

Figure 7

From: Sphingosine 1-phosphate enhances the excitability of rat sensory neurons through activation of sphingosine 1-phosphate receptors 1 and/or 3

Figure 7

VPC 23019 and VPC 44116, S1PR1/R3 antagonists and S1PR4/R5 agonists, block S1P-induced sensitization. (A) A 30-min pretreatment with 1 μM VPC 23019 blocked the capacity of 100 nM SEW2871 (SEW), a selective sphingosine-1-phosphate (S1P)R1 agonist, and 1 μM S1P, the more global agonist, to augment action potential (AP) firing in sensory neurons (P = 0.87, RM ANOVA). In contrast, in untreated neurons, SEW2871 significantly increased the number of evoked APs after only a 4-min exposure (n = 7, P < 0.001, Friedman RM ANOVA with Tukey post hoc test) although the number of evoked APs after S1P was not different from that with SEW2871. (B) In a different set of experiments, a 30-min pretreatment with 1 μM VPC 23019 blocked the sensitization produced by 1 μM S1P; however, exposure to 1 μM PGE2 significantly increased the AP firing (P < 0.05 compared to control, ANOVA followed by Holm-Sidak all-pairs test). (C) A 30-min pretreatment with 1 μM VPC 44116 blocked the sensitization produced by 1 μM S1P; however, subsequent expose to 1 μM PGE2 significantly increased the number of evoked APs compared to control (represented by asterisks (*)) as well as the number of APs measured at 10-min S1P (represented by #)(n = 5, P < 0.001, RM ANOVA with Holm-Sidak all-pairs test). Cont - control.

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