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Substance P triggers two different signaling pathways with opposing actions on M current mediated by intracellular Ca2+ rises and oxidative modification
Author(s) -
Ooi Lezanne,
Linley John,
Gamper Nikita
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb25
Subject(s) - intracellular , reactive oxygen species , microbiology and biotechnology , chemistry , cytosol , transient receptor potential channel , diacylglycerol kinase , biophysics , signal transduction , superoxide , receptor , crosstalk , oxidative phosphorylation , protein kinase c , biochemistry , biology , enzyme , physics , optics
Substance P (SP) is an important signaling molecule in pain and inflammation. Since M‐type K+ channels are critical in controlling excitability of neurons, we investigated crosstalk between M current and SP in sensory neurons from trigeminal ganglia (TG) and dorsal root ganglia (DRG). In CHO cells expressing SP receptors, SP produced a robust transient increase in cytosolic Ca2+ and translocation of probes for PIP2 and diacylglycerol indicated that SP signals through a Gq/11‐protein coupled receptor pathway. In DRG neurons SP caused significant M current augmentation, whereas TG neurons responded with both M current inhibition and augmentation. Inhibition was mediated by intracellular Ca2+ rises, whereas activation was completely reversed by the reducing agent DTT and mimicked by bath application of H2O2, suggesting this pathway is mediated by an oxidation mechanism. This was supported by imaging experiments with a reactive oxygen species‐sensitive dye and a superoxide anion probe. Thus in sensory neurons SP triggers two different signaling pathways, mediated by intracellular Ca2+ rises and reactive oxygen species, with opposing actions on M current.