Sphingosine 1-phosphate to p38 signaling via S1P1 receptor and Galphai/o evokes augmentation of capsaicin-induced ionic currents in mouse sensory neurons

In this study, the S1P mediated signaling pathway required for sensitization of TRPV1 channels was explored.The capsaicin induced peak inward current (ICAPS) of sensory neurons was significantly increased after S1P stimulation within minutes after application. The potentiation of ICAPS resulted from activation of Galphai through G-protein coupled receptors for S1P. Consequently, Galphai led to a signaling cascade, involving phosphoinositide-3-kinase (PI3K) and protein kinase C, which augmented ICAPS in nociceptive neurons. The S1P1 receptor agonist SEW2871 resulted in activation of the same signaling pathway and potentiation of ICAPS. Furthermore, the mitogen-activated protein kinase p38 was phosphorylated after S1P stimulation and inhibition of p38 signaling by SB203580 prevented the S1P-induced ICAPS potentiation. The current data suggest that S1P sensitized ICAPS through G-protein coupled S1P1 receptor activation of Galphai-PI3K-PKC-p38 signaling pathway in sensory neurons.
Source: Molecular Pain - Category: Molecular Biology Authors: Source Type: research