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Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine
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Than, Jonathan Y -X. L., Li, Lin, Hasan, Raquibul and Zhang, Xuming (2013) Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine. Journal of Biological Chemistry, 288 (18). pp. 12818-12827. doi:10.1074/jbc.M113.450072 ISSN 0021-9258.
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WRAP-TRPV1-Channel-expressing-sensory-neurons-pruritogen-chloroquine-2013.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2041Kb) | Preview |
Official URL: http://dx.doi.org/10.1074/jbc.M113.450072
Abstract
The sensations of pain, itch, and cold often interact with each other. Pain inhibits itch, whereas cold inhibits both pain and itch. TRPV1 and TRPA1 channels transduce pain and itch, whereas TRPM8 transduces cold. The pruritogen chloroquine (CQ) was reported to excite TRPA1, leading to the sensation of itch. It is unclear how CQ excites and modulates TRPA1+, TRPV1+, and TRPM8+ neurons and thus affects the sensations of pain, itch, and cold. Here, we show that only 43% of CQ-excited dorsal root ganglion neurons expressed TRPA1; as expected, the responses of these neurons were completely prevented by the TRPA1 antagonist HC-030031. The remaining 57% of CQ-excited neurons did not express TRPA1, and excitation was not prevented by either a TRPA1 or TRPV1 antagonist but was prevented by the general transient receptor potential canonical (TRPC) channel blocker BTP2 and the selective TRPC3 inhibitor Pyr3. Furthermore, CQ caused potent sensitization of TRPV1 in 51.9% of TRPV1+ neurons and concomitant inhibition of TRPM8 in 48.8% of TRPM8+ dorsal root ganglion neurons. Sensitization of TRPV1 is caused mainly by activation of the phospholipase C-PKC pathway following activation of the CQ receptor MrgprA3. By contrast, inhibition of TRPM8 is caused by a direct action of activated Gαq independent of the phospholipase C pathway. Our data suggest the involvement of the TRPC3 channel acting together with TRPA1 to mediate CQ-induced itch. CQ not only elicits itch by directly exciting itch-encoding neurons but also exerts previously unappreciated widespread actions on pain-, itch-, and cold-sensing neurons, leading to enhanced pain and itch.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 3 May 2013 | ||||
Dates: |
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Volume: | 288 | ||||
Number: | 18 | ||||
Page Range: | pp. 12818-12827 | ||||
DOI: | 10.1074/jbc.M113.450072 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 17 May 2022 | ||||
Date of first compliant Open Access: | 17 May 2022 |
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