Linley 2012 Proc Natl Acad Sci U S A: Difference between revisions
No edit summary |
No edit summary |
||
Line 30: | Line 30: | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|organism=Rat | |organism=Rat | ||
|tissues=Nervous system | |tissues=Nervous system | ||
|preparations=Intact | |preparations=Intact cells | ||
|injuries=RONS; Oxidative Stress | |||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
|instruments=Oxygraph-2k | |||
}} | }} |
Revision as of 08:44, 8 August 2013
Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gampera N (2012) Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proc Natl Acad Sci U S A 109: 1578-1586 |
Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gampera N (2012) Proc Natl Acad Sci U S A
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 Gi/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 Ca2+ stores. In rats SP causes sensitization of TRPV1 and produces thermal hyperalgesia. However, the lack of coupling between SP signaling and inositol 1,4,5-trisphosphate sensitive Ca2+ stores, together with the augmenting effect on M channels, renders the SP pathway ineffective to excite nociceptors acutely and produce spontaneous pain. Our study describes a mechanism for neurokinin signaling in sensory neurons and provides evidence that spontaneous pain and hyperalgesia can have distinct underlying mechanisms within a single nociceptive neuron. โข Keywords: Dorsal root ganglia
โข O2k-Network Lab: UK Leeds Peers C
Labels:
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Rat Tissue;cell: Nervous system Preparation: Intact cells
Coupling state: OXPHOS
HRR: Oxygraph-2k