RGD Reference Report - Proteinase-activated receptor-4 (PAR4) activation leads to sensitization of rat joint primary afferents via a bradykinin B2 receptor-dependent mechanism. - Rat Genome Database

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Proteinase-activated receptor-4 (PAR4) activation leads to sensitization of rat joint primary afferents via a bradykinin B2 receptor-dependent mechanism.

Authors: Russell, FA  Veldhoen, VE  Tchitchkan, D  McDougall, JJ 
Citation: Russell FA, etal., J Neurophysiol. 2010 Jan;103(1):155-63. doi: 10.1152/jn.00486.2009. Epub 2009 Nov 4.
RGD ID: 9835339
Pubmed: PMID:19889854   (View Abstract at PubMed)
DOI: DOI:10.1152/jn.00486.2009   (Journal Full-text)

The G-protein-linked receptor, proteinase-activated receptor-4 (PAR(4)) is activated by proteinases released into the joint during inflammation. It is unclear whether PAR(4) has a pro- or anti-nociceptive effect and whether it directly affects nerve activity. In this study, we examined the expression of PAR(4) in joints and dorsal root ganglion (DRG) neurons and whether activation of PAR(4) has an effect on nociception in normal rat knee joints. Electrophysiological recordings were made from joint primary afferents in male Wistar rats during both nonnoxious and noxious rotations of the knee. Afferent firing rate was recorded for 15 min post close intra-arterial injection of 10(-9)-10(-5) mol of the PAR(4) activating peptide, AYPGKF-NH(2), or the inactive peptide, YAPGKF-NH(2) (100 mul bolus). Rats were either naive or pretreated with the selective PAR(4) antagonist, pepducin P4pal-10, the transient receptor potential vanilloid-1 (TRPV1) antagonist, SB366791, or the bradykinin B(2) receptor antagonist, HOE140. Immunofluorescence experiments showed extensive PAR(4) expression in the knee joint and in sensory neurons projecting from the joint. AYPGKF-NH(2) significantly increased joint afferent firing during nonnoxious and noxious rotation of the knee. The inactive control peptide, YAPGKF-NH(2) was without effect. Systemic pretreatment with the PAR(4) antagonist, pepducin P4pal-10, inhibited the AYPGKF-NH(2)-induced increase in firing rate. Pretreatment with HOE140, but not SB366791, also blocked this increase in firing rate. These data reveal that in normal rat knee joints, PAR(4) activation increases joint primary afferent activity in response to mechanical stimuli. This PAR(4)-induced sensitization is TRPV1-independent but involves B(2) receptor activation, suggesting a role for kinins in this process.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PawrRatpositive regulation of neuronal action potential  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pawr  (pro-apoptotic WT1 regulator)


Additional Information