Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons.

ABSTRACT: Substance P (SP) is a prominent neuromodulator, which is produced and released by peripheral damage-sensing (nociceptive) neurons; these neurons also express SP receptors. However, the mechanisms of peripheral SP signaling are poorly understood. We report a signaling pathway of SP in nociceptive neurons: Acting predominantly through NK1 receptors and G(i/o) proteins, SP stimulates increased release of reactive oxygen species from the mitochondrial electron transport chain. Reactive oxygen species, functioning as second messengers, induce oxidative modification and augment M-type potassium channels, thereby suppressing excitability. This signaling cascade requires activation of phospholipase C but is largely uncoupled from the inositol 1,4,5-trisphosphate sensitive Ca(2+) stores. In rats SP

SUBMITTER: Linley JE 

PROVIDER: S-EPMC3386117 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature