The FASEB journal, 2009-04, Vol.23 (4), p.1102-1114
2009
Details
- Autor(en) / Beteiligte
- Titel
- Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases
- Ist Teil von
- The FASEB journal, 2009-04, Vol.23 (4), p.1102-1114
- Ort / Verlag
- United States: The Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- 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 Ca²⁺ imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca²⁺ 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.--Bessac, B. F., Sivula, M., von Hehn, C. A., Caceres, A. I., Escalera, J., Jordt, S.-E. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.08-117812Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2660642
- Format
- –
- Schlagworte
- analgesia, Animals, Cell Line, Cells, Cultured, CHO Cells, Cricetinae, Cricetulus, Dose-Response Relationship, Drug, Electrophysiology, Female, Ganglia, Spinal - cytology, Ganglia, Spinal - drug effects, Ganglia, Spinal - metabolism, Hypochlorous Acid - pharmacology, Isocyanates - toxicity, Kidney - cytology, Kidney - embryology, Male, Mice, Mice, Inbred C57BL, Neurons, Afferent - cytology, Neurons, Afferent - drug effects, Neurons, Afferent - metabolism, nociception, Oxidants - pharmacology, pain, Patch-Clamp Techniques, Research Communications, sensory neurons, Tear Gases - toxicity, Transient Receptor Potential Channels - antagonists & inhibitors, Transient Receptor Potential Channels - genetics, Trigeminal Ganglion - cytology, Trigeminal Ganglion - drug effects, Trigeminal Ganglion - metabolism, TRP channels, TRPA1 Cation Channel