| Autor: |
Jing Wu, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ping Ren, Ming Jiao, Wang-Ping Hu |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-11 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1742-2094 |
| DOI: |
10.1186/s12974-017-0916-4 |
| Popis: |
Abstract Background Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception. Methods Electrophysiological experiments were performed on both rat DRG neurons and Chinese hamster ovary (CHO) cells expressing ASIC3 and PAR2. Nociceptive behavior was induced by acetic acid in rats. Results PAR2-AP, PAR2-activating peptide, concentration-dependently increased the ASIC3 currents in CHO cells transfected with ASIC3 and PAR2. The proton concentration–response relationship was not changed, but that the maximal response increased 58.7 ± 3.8% after pretreatment of PAR2-AP. PAR2 mediated the potentiation of ASIC3 currents via an intracellular cascade. PAR2-AP potentiation of ASIC3 currents disappeared after inhibition of intracellular G protein, PLC, PKC, or PKA signaling. Moreover, PAR2 activation increased proton-evoked currents and spikes mediated by ASIC3 in rat dorsal root ganglion neurons. Finally, peripheral administration of PAR2-AP dose-dependently exacerbated acidosis-induced nocifensive behaviors in rats. Conclusions These results indicated that PAR2 signaling sensitized ASIC3, which may contribute to acidosis-induced nociception. These represent a novel peripheral mechanism underlying PAR2 involvement in hyperalgesia by sensitizing ASIC3 in primary sensory neurons. |
| Databáze: |
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| Externí odkaz: |
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