1. Sanguinarine is an agonist of TRPA1 channel.
- Author
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Chi H, Zhang X, Chen X, Fang S, Ding Q, and Gao Z
- Subjects
- Animals, Calcium metabolism, Cells, Cultured, HEK293 Cells, Humans, Mice, Knockout, Nociceptive Pain chemically induced, Sensory Receptor Cells drug effects, Sensory Receptor Cells metabolism, Sensory Receptor Cells physiology, TRPA1 Cation Channel antagonists & inhibitors, TRPA1 Cation Channel genetics, Mice, Benzophenanthridines pharmacology, Isoquinolines pharmacology, TRPA1 Cation Channel agonists
- Abstract
Sanguinarine, a benzyl isoquinoline alkaloid extracted from the root of Papaveraceae plants, shows extensive pharmacological activities including anti-microbial, anti-trypanosoma, anti-tumor, anti-platelet, anti-hypertensive effects, as well as inhibition of osteoclast formation. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) is a potential target for sanguinarine. Electrophysiological recordings show that sanguinarine activates TRPA1 channel potently with an EC
50 0.09 (0.04-0.13) μM, but has no effects on other examined TRP channels. Sanguinarine increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion (DRG) neurons in vitro significantly. Plantar injection of sanguinarine evokes nociceptive behaviors similar to that elicited by allyl isothiocyanate (AITC), a classic agonist of TRPA1. Both the enhancement of excitability of DRG neurons and the nociceptive behaviors can be attenuated by treatment of TRPA1 channel antagonist HC030031 or knockout of trpa1 gene. Taken together, our data demonstrate that sanguinarine is a potent and relatively selective agonist of TRPA1 channel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)- Published
- 2021
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