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Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin.
Am J Physiol Cell Physiol. 2013 Feb 15; 304(4):C354-61.AJ

Abstract

Gold compounds, which were widely used to treat rheumatoid arthritis, have been recently used as experimental agents for tumor treatment. Transient receptor potential (TRP) ankyrin repeat 1 (TRPA1) is a Ca(2+)-permeable ion channel that senses acute and inflammatory pain signals. Electrophilic compounds such as mustard oil and cinnamaldehyde activate TRPA1 by interacting with TRPA1 cysteine residues. Here we investigate the effects of the gold compound auranofin (AUR) on TRPA1 channels. Intracellular Ca(2+) and whole cell patch-clamp recordings were performed on human embryonic kidney cells transiently expressed with TRPA1, TRP melastatin 8 (TRPM8), and vanilloid type TRP (TRPV1-4) channels. AUR stimulated TRPA1 in a concentration-dependent manner with a half-maximum potency of around 1.0 μM. The AUR-induced response was effectively blocked by HC030031, a TRPA1 antagonist. On the other hand, AUR failed to activate TRPM8 and TRPV1-4 channels, which are highly expressed in sensory neurons as nociceptors. The stimulatory effect on TRPA1 channels depended on the C414, C421, C621, and C633 cysteine residues and not on the inhibition of thioredoxin reductase by AUR. Moreover, AUR effectively activated TRPA1 channels expressed in human differentiated neuroblastoma cell lines. The study shows that AUR is a potent stimulator of TRPA1 channels.

Authors+Show Affiliations

Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23220116

Citation

Hatano, Noriyuki, et al. "Stimulation of Human TRPA1 Channels By Clinical Concentrations of the Antirheumatic Drug Auranofin." American Journal of Physiology. Cell Physiology, vol. 304, no. 4, 2013, pp. C354-61.
Hatano N, Suzuki H, Muraki Y, et al. Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin. Am J Physiol Cell Physiol. 2013;304(4):C354-61.
Hatano, N., Suzuki, H., Muraki, Y., & Muraki, K. (2013). Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin. American Journal of Physiology. Cell Physiology, 304(4), C354-61. https://doi.org/10.1152/ajpcell.00096.2012
Hatano N, et al. Stimulation of Human TRPA1 Channels By Clinical Concentrations of the Antirheumatic Drug Auranofin. Am J Physiol Cell Physiol. 2013 Feb 15;304(4):C354-61. PubMed PMID: 23220116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin. AU - Hatano,Noriyuki, AU - Suzuki,Hiroka, AU - Muraki,Yukiko, AU - Muraki,Katsuhiko, Y1 - 2012/12/05/ PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/4/9/medline SP - C354 EP - 61 JF - American journal of physiology. Cell physiology JO - Am J Physiol Cell Physiol VL - 304 IS - 4 N2 - Gold compounds, which were widely used to treat rheumatoid arthritis, have been recently used as experimental agents for tumor treatment. Transient receptor potential (TRP) ankyrin repeat 1 (TRPA1) is a Ca(2+)-permeable ion channel that senses acute and inflammatory pain signals. Electrophilic compounds such as mustard oil and cinnamaldehyde activate TRPA1 by interacting with TRPA1 cysteine residues. Here we investigate the effects of the gold compound auranofin (AUR) on TRPA1 channels. Intracellular Ca(2+) and whole cell patch-clamp recordings were performed on human embryonic kidney cells transiently expressed with TRPA1, TRP melastatin 8 (TRPM8), and vanilloid type TRP (TRPV1-4) channels. AUR stimulated TRPA1 in a concentration-dependent manner with a half-maximum potency of around 1.0 μM. The AUR-induced response was effectively blocked by HC030031, a TRPA1 antagonist. On the other hand, AUR failed to activate TRPM8 and TRPV1-4 channels, which are highly expressed in sensory neurons as nociceptors. The stimulatory effect on TRPA1 channels depended on the C414, C421, C621, and C633 cysteine residues and not on the inhibition of thioredoxin reductase by AUR. Moreover, AUR effectively activated TRPA1 channels expressed in human differentiated neuroblastoma cell lines. The study shows that AUR is a potent stimulator of TRPA1 channels. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/23220116/Stimulation_of_human_TRPA1_channels_by_clinical_concentrations_of_the_antirheumatic_drug_auranofin_ L2 - https://journals.physiology.org/doi/10.1152/ajpcell.00096.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -