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Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS
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Jun Chen, Genentech
This is a very interesting
This is a very interesting paper, which addresses the role of TRPA1 channel in thermoregulation. Here are several aspects I would like to highlight:
First, the authors report that TRPA1 does not contribute to cold defenses in rodents. Previously the same group reported functions for two other TRP channels: TRPM8 mediates cold-induced tail vasoconstriction and brown adipose tissue (BAT) thermogenesis, and TRPV1 tonically suppresses autonomic cold defenses. Therefore, as a protein class, TRP channels exhibit a spectrum of effects on thermoregulation.
Second, the current study employed a comprehensive approach—a combination of gene knockout and pharmacology tools, since gene knockout data could be confounded by compensatory/developmental mechanisms and pharmacological studies could be complicated by lack of selectivity or drug exposure. In pharmacological studies, the authors used two antagonists from different chemical classes, and demonstrated drug exposures and receptor coverage (i.e., AITC-induced pain). These efforts made their conclusions very convincing.
Third, the current study, along with our previous report (Chen et al., 2011), suggests that TRPA1 antagonists do not cause hyperthermia (like TRPV1 antagonists), or hypothermia (like TRPM8 antagonists). This is great news to current efforts pursuing TRPA1 antagonists as therapeutics.
Fourth, the rapid progress in delineating the role of TRP channels in thermoregulation has been made, in large part, by the same groups of researchers (i.e., Romanovsky’s group at St. Joseph’s Hospital and Medical Center and Gavva’s group at Amgen [both of which are authors on the current paper]). I am glad that my former colleagues at Abbvie (Mike Kort and Phil Kym [also authors on the current paper]) joined this productive academia-industry alliance. Without doubt, such alliance will afford unique research opportunities.