NDLI: Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner

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Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Komatsu, Tomoko Uchida, Kunitoshi Fujita, Fumitaka Zhou, Yiming Tominaga, Makoto
Description	Country affiliation: Japan Author Affiliation: Komatsu T ( Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi, Japan.)
Abstract	Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is mainly expressed in primary nociceptive neurons. TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent compounds such as mustard oil and cinnamaldehyde, and intracellular alkalization. Here, we show that primary alcohols, which have been reported to cause skin, eye or nasal irritation, activate human TRPA1 (hTRPA1). We measured intracellular Ca(2+) changes in HEK293 cells expressing hTRPA1 induced by 1 mM primary alcohols. Higher alcohols (1-butanol to 1-octanol) showed Ca(2+) increases proportional to the carbon chain length. In whole-cell patch-clamp recordings, higher alcohols (1-hexanol to 1-octanol) activated hTRPA1 and the potency increased with the carbon chain length. Higher alcohols evoked single-channel opening of hTRPA1 in an inside-out configuration. In addition, cysteine at 665 in the N terminus and histidine at 983 in the C terminus were important for hTRPA1 activation by primary alcohols. Furthermore, straight-chain secondary alcohols increased intracellular Ca(2+) concentrations in HEK293 cells expressing hTRPA1, and both primary and secondary alcohols showed hTRPA1 activation activities that correlated highly with their octanol/water partition coefficients. On the other hand, mouse TRPA1 did not show a strong response to 1-hexanol or 1-octanol, nor did these alcohols evoke significant pain in mice. We conclude that primary and secondary alcohols activate hTRPA1 in a carbon chain length-dependent manner. TRPA1 could be a sensor of alcohols inducing skin, eye and nasal irritation in human.
File Format	HTM / HTML
ISSN	00316768
Issue Number	4
Volume Number	463
e-ISSN	14322013
Journal	Pflügers Archiv - European Journal of Physiology
Language	English
Publisher	Springer
Publisher Date	2012-04-01
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Physiology Alcohols Chemistry Pharmacology Calcium Channels Analysis Metabolism Nerve Tissue Proteins Transient Receptor Potential Channels Drug Effects 1-butanol 1-octanol Animals Calcium Genetics Cell Line Cells, Cultured Hek293 Cells Hexanols Humans Membrane Potentials Physiology Mice Mice, Inbred C57bl Mice, Knockout Molecular Structure Mutation Neurons Patch-clamp Techniques Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner

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Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner