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Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

Publication ,  Journal Article
Bessac, BF; Sivula, M; von Hehn, CA; Caceres, AI; Escalera, J; Jordt, S-E
Published in: FASEB J
April 2009

The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2009

Volume

23

Issue

4

Start / End Page

1102 / 1114

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Transient Receptor Potential Channels
  • Tear Gases
  • TRPA1 Cation Channel
  • Patch-Clamp Techniques
  • Oxidants
  • Neurons, Afferent
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

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Bessac, B. F., Sivula, M., von Hehn, C. A., Caceres, A. I., Escalera, J., & Jordt, S.-E. (2009). Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J, 23(4), 1102–1114. https://doi.org/10.1096/fj.08-117812
Bessac, Bret F., Michael Sivula, Christian A. von Hehn, Ana I. Caceres, Jasmine Escalera, and Sven-Eric Jordt. “Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.FASEB J 23, no. 4 (April 2009): 1102–14. https://doi.org/10.1096/fj.08-117812.
Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt S-E. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J. 2009 Apr;23(4):1102–14.
Bessac, Bret F., et al. “Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.FASEB J, vol. 23, no. 4, Apr. 2009, pp. 1102–14. Pubmed, doi:10.1096/fj.08-117812.
Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt S-E. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J. 2009 Apr;23(4):1102–1114.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2009

Volume

23

Issue

4

Start / End Page

1102 / 1114

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Transient Receptor Potential Channels
  • Tear Gases
  • TRPA1 Cation Channel
  • Patch-Clamp Techniques
  • Oxidants
  • Neurons, Afferent
  • Mice, Inbred C57BL
  • Mice
  • Male