| Project/Area Number |
20602017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
疼痛学
|
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| Research Institution | Hyogo University of Health Sciences |
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Principal Investigator |
DAI Yi Hyogo University of Health Sciences, 薬学部, 准教授 (20330441)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | TRPA1 / P2X3 / PAIN / Inflammation / TRA1 / inflammation / PKA / PKC / pain / DRG / ATP / PAR2 / neuron |
|---|
| Research Abstract |
The TRPA1/P2X3 ion channel is localized on nociceptors of sensory neurons. Both bradykinin receptor 2 (B2R) or Proteinase-activated receptor-2 (PAR-2) are expressed in a subset of primary afferent neurons and is involved in inflammatory nociception. In this study, the functional interaction of the B2R or PAR-2 and TRPA1/P2X3, was investigated by morphological, molecular-biological and electrophysiological analyses in rat dorsal root ganglion (DRG) neurons or HEK cells transfected with TRPA1 or P2X_3. We found that many TRPA1s or P2X_3s were functionally co-expressed with the B2R or PAR-2 in rat DRG neurons. Using whole-cell patch clamp technique, we observed that B2R/PAR-2 activation increased the TRPA1/P2X currents evoked by allyl isothiocyanate or alpha beta-methylene adenosine 5'-triphosphate in DRG neurons, respectively. Inhibitors of phospholipase C (PLC), or protein kinase A (PKA) suppressed these potentiations. Application of a PLC activator or a PKA activator mimicked the B2R/PAR-2 mediated potentiation of TRPA1 or P2X current, respectively. Thus, the increased TRPA1 or P2X sensitivity may be due to the activation of PLC and/or PKA, which are downstream of the B2R and PAR-2 signal. These findings indicate that in inflammatory disease, Bradykinin or PAR-2 agonists may potentiate TRPA1 or P2X_3 ion channels to induce pain ; the mechanism of this potentiation is likely to be a result of activation of PLC or PKA signals.
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