| RRC ID |
59730
|
| 著者 |
Miyano K, Shiraishi S, Minami K, Sudo Y, Suzuki M, Yokoyama T, Terawaki K, Nonaka M, Murata H, Higami Y, Uezono Y.
|
| タイトル |
Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.
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| 巻・号 |
20(13)
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| 公開日 |
2019-7-3
|
| DOI |
10.3390/ijms20133271
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| PII |
ijms20133271
|
| PMID |
31277262
|
| PMC |
PMC6651390
|
| MeSH |
A Kinase Anchor Proteins / metabolism
Animals
Carboplatin / adverse effects
Carboplatin / pharmacology*
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Humans
Hyperalgesia / chemically induced*
Hyperalgesia / metabolism
Male
Mice
Mice, Inbred C57BL
Signal Transduction*
TRPA1 Cation Channel / metabolism*
|
| IF |
4.183
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
