Linked Life Data

17978048

Source:http://linkedlifedata.com/resource/pubmed/id/17978048

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2007-11-5
pubmed:abstractText
The neuropeptide substance P (SP) is expressed in unmyelinated primary sensory neurons and represents the best known "pain" neurotransmitter. It is generally believed that SP regulates pain transmission and sensitization by acting on neurokinin-1 receptor (NK-1), which is expressed in postsynaptic dorsal horn neurons. However, the expression and role of NK-1 in primary sensory neurons are not clearly characterized. Our data showed that NK-1 was expressed in both intact and dissociated dorsal root ganglion (DRG) neurons. In particular, NK-1 was mainly coexpressed with the capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1), a critical receptor for the generation of heat hyperalgesia. NK-1 agonist [Sar(9), Met(O2)(11)]-substance P (Sar-SP) significantly potentiated capsaicin-induced currents and increase of [Ca2+]i in dissociated DRG neurons. NK-1 antagonist blocked not only the potentiation of TRPV1 currents but also heat hyperalgesia induced by intraplantar Sar-SP. NK-1 antagonist also inhibited capsaicin-induced spontaneous pain, and this inhibition was enhanced after inflammation. To analyze intracellular cross talking of NK-1 and TRPV1, we examined downstream signal pathways of G-protein-coupled NK-1 activation. Sar-SP-induced potentiation of TRPV1 was blocked by inhibition of G-protein, PLCbeta (phospholipase C-beta), or PKC but not by inhibition of PKA (protein kinase A). In particular, PKCepsilon inhibitor completely blocked both Sar-SP-induced TRPV1 potentiation and heat hyperalgesia. Sar-SP also induced membrane translocation of PKCepsilon in a portion of small DRG neurons. These results reveal a novel mechanism of NK-1 in primary sensory neurons via a possible autocrine and paracrine action of SP. Activation of NK-1 in these neurons induces heat hyperalgesia via PKCepsilon-mediated potentiation of TRPV1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12067-77
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17978048-Analysis of Variance, pubmed-meshheading:17978048-Animals, pubmed-meshheading:17978048-Animals, Newborn, pubmed-meshheading:17978048-Behavior, Animal, pubmed-meshheading:17978048-Calcium, pubmed-meshheading:17978048-Dose-Response Relationship, Drug, pubmed-meshheading:17978048-Electric Stimulation, pubmed-meshheading:17978048-Enzyme Inhibitors, pubmed-meshheading:17978048-Ganglia, Spinal, pubmed-meshheading:17978048-Hyperalgesia, pubmed-meshheading:17978048-Male, pubmed-meshheading:17978048-Membrane Potentials, pubmed-meshheading:17978048-Nerve Tissue Proteins, pubmed-meshheading:17978048-Neurons, Afferent, pubmed-meshheading:17978048-Patch-Clamp Techniques, pubmed-meshheading:17978048-Peptide Fragments, pubmed-meshheading:17978048-Protein Kinase C-epsilon, pubmed-meshheading:17978048-Rats, pubmed-meshheading:17978048-Rats, Sprague-Dawley, pubmed-meshheading:17978048-Receptors, Neurokinin-1, pubmed-meshheading:17978048-Substance P, pubmed-meshheading:17978048-TRPV Cation Channels
pubmed:year
2007
pubmed:articleTitle
Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia.
pubmed:affiliation
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural