Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases
| Autor: | Michael Sivula, Bret F. Bessac, Jasmine Escalera, Ana Isabel Caceres, Sven-Eric Jordt, Christian A. A. von Hehn |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Patch-Clamp Techniques CHO Cells Methyl isocyanate Pharmacology medicine.disease_cause Kidney Tear Gases Biochemistry Cell Line chemistry.chemical_compound Transient receptor potential channel Tear gas Mice Cricetulus Transient Receptor Potential Channels In vivo Edema Cricetinae Ganglia Spinal Genetics medicine Animals Neurons Afferent Molecular Biology TRPA1 Cation Channel Cells Cultured Dose-Response Relationship Drug Oxidants Isocyanate Hypochlorous Acid Electrophysiology Mice Inbred C57BL chemistry Trigeminal Ganglion Anesthesia Female Irritation medicine.symptom Biotechnology Isocyanates |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 23(4) |
| ISSN: | 1530-6860 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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