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

Molecular Pain

Norbert Mair²  Michaela Kress²  Michael G Leitner¹  Serena Quarta²  Michiel Langeslag² 

[1] Department of Neurophysiology, Institute for Physiology and Pathophysiology, Philipps University of Marburg, Marburg, Germany;Division Physiology, DPMP, Medical University Innsbruck, Fritz-Pregl-Str. 3-I, 6020 Innsbruck, Austria

关键词: MAP-kinase p38;    Phosphoinositide 3-kinase;    Gαi;    Capsaicin;    TRPV1;    Sphingosine 1-phosphate;   

Others  :  1135556
DOI  :  10.1186/1744-8069-10-74

 received in 2014-07-08, accepted in 2014-11-03,  发布年份 2014

【 摘 要 】

The perception of painful thermal stimuli by sensory neurons is largely mediated by TRPV1. Upon tissue injury or inflammation, S1P is secreted by thrombocytes as part of an inflammatory cocktail, which sensitizes nociceptive neurons towards thermal stimuli. S1P acts on G-protein coupled receptors that are expressed in sensory neurons and sensitize TRPV1 channels towards thermal stimuli. In this study, the S1P mediated signaling pathway required for sensitization of TRPV1 channels was explored.

The capsaicin induced peak inward current (I_CAPS) of sensory neurons was significantly increased after S1P stimulation within minutes after application. The potentiation of I_CAPS resulted from activation of Gαi through G-protein coupled receptors for S1P. Consequently, Gαi led to a signaling cascade, involving phosphoinositide-3-kinase (PI₃K) and protein kinase C, which augmented I_CAPS in nociceptive neurons. The S1P₁ receptor agonist SEW2871 resulted in activation of the same signaling pathway and potentiation of I_CAPS. Furthermore, the mitogen-activated protein kinase p38 was phosphorylated after S1P stimulation and inhibition of p38 signaling by SB203580 prevented the S1P-induced I_CAPS potentiation. The current data suggest that S1P sensitized I_CAPS through G-protein coupled S1P₁ receptor activation of Gαi-PI₃K-PKC-p38 signaling pathway in sensory neurons.

【 授权许可】

   
2014 Langeslag et al.; licensee BioMed Central Ltd.

【 图 表 】

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