Advertisement

Involvement of TRPV1-ANO1 Interactions in Pain-Enhancing Mechanisms

  • Y. Takayama
  • Makoto Tominaga
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1099)

Abstract

Primary sensory neurons detect potentially dangerous environmental situations via many “sensor” proteins located on the plasma membrane. Although receptor-type cation channels are thought to be the major sensors in sensory neurons, anion channels are also important players in the peripheral nervous system. Recently, we showed that transient receptor potential vanilloid 1 (TRPV1) interacts with anoctamin 1 (ANO1, also called TMEM16A) in primary sensory neurons and that this interaction enhanced TRPV1-mediated pain sensation. In that study, we induced ANO1 currents by application of capsaicin to small DRG neurons and showed that ANO1-dependent depolarization following TRPV1 activation could evoke more action potentials. Furthermore, capsaicin-evoked pain-related behaviors in mice were strongly inhibited by a selective ANO1 blocker. Together these findings indicate that selective ANO1 inhibition can reduce pain sensation. We also investigated non-specific inhibitory effects on ion channel activities to control ion dynamics via the TRPV1-ANO1 complex. We found that 4-isopropylcyclohexanol (4-iPr-CyH-OH) had an analgesic effect on burning pain sensations through its inhibition of TRPV1 and ANO1 together. Additionally, 4-iPr-CyH-OH did not have clear agonistic effects on TRPV1, TRPA1, and ANO1 activity individually. These results indicate that 4-iPr-CyH-OH could function globally to mediate TRP-ANO1 complex functions to reduce skin hypersensitivity and could form the basis for novel analgesic agents.

Keywords

TRP channel Anoctamin 1 Isopropylcyclohexanol Acute pain 

Notes

Acknowledgments

Our study is supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan, the Kato Memorial Bioscience Foundation, and the Takeda Science Foundation.

References

  1. 1.
    Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322:590–594CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, Back SK, Na HS, Harfe BD, Wang F, Raouf R, Wood JN, Oh U (2012) The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 15:1015–1021CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Cho H, Oh U (2013) Anoctamin 1 mediates thermal pain as a heat sensor. Curr Neuropharmacol 11:641–651CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Crutzen R, Virreira M, Markadieu N, Shlyonsky V, Sener A, Malaisse WJ, Beauwens R, Boom A, Golstein PE (2016) Anoctamin 1 (Ano1) is required for glucose-induced membrane potential oscillations and insulin secretion by murine beta-cells. Pflugers Arch 468:573–591CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbuhler K, Ye W, Qi L, Chen T, Craik CS, Nung Jan Y, Minor DL Jr, Cheng Y, Yeh Jan L (2017) Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature 552:426–429CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Derouiche S, Takayama Y, Murakami M, Tominaga M (2018) TRPV4 heats up ANO1-dependent exocrine gland fluid secretion. FASEB J 32:1841–1854 fj201700954RCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Dibattista M, Amjad A, Maurya DK, Sagheddu C, Montani G, Tirindelli R, Menini A (2012) Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons. J Gen Physiol 140:3–15CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Ferrera L, Caputo A, Ubby I, Bussani E, Zegarra-Moran O, Ravazzolo R, Pagani F, Galietta LJ (2009) Regulation of TMEM16A chloride channel properties by alternative splicing. J Biol Chem 284:33360–33368CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Gees M, Colsoul B, Nilius B (2010) The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol 2:a003962CrossRefPubMedCentralGoogle Scholar
  10. 10.
    Henningsen GM, Salomon RA, Yu KO, Lopez I, Roberts J, Serve MP (1988) Metabolism of nephrotoxic isopropylcyclohexane in male Fischer 344 rats. J Toxicol Environ Health 24:19–25CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Jin X, Shah S, Liu Y, Zhang H, Lees M, Fu Z, Lippiat JD, Beech DJ, Sivaprasadarao A, Baldwin SA, Zhang H, Gamper N (2013) Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor. Sci Signal 6:ra73CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Jin X, Shah S, Du X, Zhang H, Gamper N (2016) Activation of Ca(2+) -activated Cl(−) channel ANO1 by localized Ca(2+) signals. J Physiol 594:19–30CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Julius D (2013) TRP channels and pain. Annu Rev Cell Dev Biol 29:355–384CrossRefGoogle Scholar
  14. 14.
    Kanju P, Chen Y, Lee W, Yeo M, Lee SH, Romac J, Shahid R, Fan P, Gooden DM, Simon SA, Spasojevic I, Mook RA, Liddle RA, Guilak F, Liedtke WB (2016) Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep 6:26894CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kim S, Kang C, Shin CY, Hwang SW, Yang YD, Shim WS, Park MY, Kim E, Kim M, Kim BM, Cho H, Shin Y, Oh U (2006) TRPV1 recapitulates native capsaicin receptor in sensory neurons in association with Fas-associated factor 1. J Neurosci 26:2403–2412CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kunzelmann K, Kongsuphol P, Aldehni F, Tian Y, Ousingsawat J, Warth R, Schreiber R (2009) Bestrophin and TMEM16-Ca(2+) activated Cl(−) channels with different functions. Cell Calcium 46:233–241CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–112CrossRefPubMedCentralGoogle Scholar
  18. 18.
    Liu B, Linley JE, Du X, Zhang X, Ooi L, Zhang H, Gamper N (2010) The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+−activated Cl- channels. J Clin Invest 120:1240–1252CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Magori N, Fujita T, Kumamoto E (2018) Hinokitiol inhibits compound action potentials in the frog sciatic nerve. Eur J Pharmacol 819:254–260CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Mao S, Garzon-Muvdi T, Di Fulvio M, Chen Y, Delpire E, Alvarez FJ, Alvarez-Leefmans FJ (2012) Molecular and functional expression of cation-chloride cotransporters in dorsal root ganglion neurons during postnatal maturation. J Neurophysiol 108:834–852CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Maruyama K, Takayama Y, Kondo T, Ishibashi KI, Sahoo BR, Kanemaru H, Kumagai Y, Martino MM, Tanaka H, Ohno N, Iwakura Y, Takemura N, Tominaga M, Akira S (2017) Nociceptors boost the resolution of fungal osteoinflammation via the TRP channel-CGRP-Jdp2 axis. Cell Rep 19:2730–2742CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Mulier M, Vriens J, Voets T (2017) TRP channel pores and local calcium signals. Cell Calcium 66:19–24CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Paulino C, Kalienkova V, Lam AKM, Neldner Y, Dutzler R (2017) Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM. Nature 552:421–425CrossRefPubMedCentralGoogle Scholar
  24. 24.
    Pedemonte N, Galietta LJ (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Schreiber R, Uliyakina I, Kongsuphol P, Warth R, Mirza M, Martins JR, Kunzelmann K (2010) Expression and function of epithelial anoctamins. J Biol Chem 285:7838–7845CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Schroeder BC, Cheng T, Jan YN, Jan LY (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Suzuki J, Fujii T, Imao T, Ishihara K, Kuba H, Nagata S (2013) Calcium-dependent phospholipid scramblase activity of TMEM16 protein family members. J Biol Chem 288:13305–13316CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Takaishi M, Uchida K, Suzuki Y, Matsui H, Shimada T, Fujita F, Tominaga M (2016) Reciprocal effects of capsaicin and menthol on thermosensation through regulated activities of TRPV1 and TRPM8. J Physiol Sci 66:143–155CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Takayama Y, Shibasaki K, Suzuki Y, Yamanaka A, Tominaga M (2014) Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1. FASEB J 28:2238–2248CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Takayama Y, Uta D, Furue H, Tominaga M (2015) Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons. Proc Natl Acad Sci U S A 112:5213–5218CrossRefPubMedCentralGoogle Scholar
  31. 31.
    Takayama Y, Furue H, Tominaga M (2017) 4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities. Sci Rep 7:43132CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci U S A 98:6951–6956CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Viitanen TM, Sukumaran P, Lof C, Tornquist K (2013) Functional coupling of TRPC2 cation channels and the calcium-activated anion channels in rat thyroid cells: implications for iodide homeostasis. J Cell Physiol 228:814–823CrossRefPubMedCentralGoogle Scholar
  34. 34.
    Vriens J, Nilius B, Voets T (2014) Peripheral thermosensation in mammals. Nat Rev Neurosci 15:573–589CrossRefPubMedCentralGoogle Scholar
  35. 35.
    Wang Q, Leo MD, Narayanan D, Kuruvilla KP, Jaggar JH (2016) Local coupling of TRPC6 to ANO1/TMEM16A channels in smooth muscle cells amplifies vasoconstriction in cerebral arteries. Am J Phys Cell Phys 310:C1001–C1009CrossRefGoogle Scholar
  36. 36.
    Xu Z, Lefevre GM, Gavrilova O, Foster St Claire MB, Riddick G, Felsenfeld G (2014) Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion. Proc Natl Acad Sci U S A 111:16760–16765CrossRefPubMedCentralGoogle Scholar
  37. 37.
    Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215CrossRefPubMedCentralGoogle Scholar
  38. 38.
    Zhang X, Li L, McNaughton PA (2008) Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 59:450–461CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Division of Cell SignalingOkazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences)OkazakiJapan

Personalised recommendations