TRPA Assays
Background of TRPA
TRPA was first named ANKTM1 since it has many N-terminal ankyrin repeats. TRPA1 is the only member of the TRPA family in mammals, while there are two and four TRPA members in C. elegans and Drosophila, respectively. This single mammalian member of the TRPA subfamily is highly co-expressed with TRPV1 in nociceptor neurons and was initially described as a noxious cold sensor, although its role in cold sensing in mice and humans remains a matter of debate. In contrast, the role of TRPA1 in nociceptive responses to chemical compounds is well established.
Fig. 1. Structure of transient receptor potential ankyrin 1 (TRPA1). (Bamps, 2021)
Distribution and Function of TRPA
TRPA1 is found in the plasma membrane of pain-detecting sensory nerves and activates pain pathways that trigger avoidance behaviors and pathways that promote long-lasting responses, such as inflammation. Blocking the TRPA1 function is therefore a promising strategy to reduce pain.
Mechanisms and Diseases of TRPA
TRPA1 can be activated by a wide variety of irritants, which include numerous natural pungent like cinnamaldehyde, responsible for the flavor and odor of cinnamon; allicin, present in garlic; and allyl isothiocyanate, the pungent ingredient in wasabi and mustard oil. All of these compounds activate TRPA1 through the covalent modification of reactive cysteine and lysine residues in the channel's N terminus. Moreover, multiple endogenous compounds released under conditions of oxidative stress and inflammation have been described to activate TRPA1, evidently pointing toward a role of the channel in nociception and pathological pain. This has been confirmed in several animal models that showed the effects of genetic ablation or pharmacological inhibition of TRPA1 in inflammatory pain as well as in diabetic and chemotherapy-induced painful neuropathy.
Assay List of TRPA Channel
Creative Biolabs can provide a range of assays of the TRPA channel. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | A dual receptors-targeting and size-switchable "cluster bomb" co-loading chemotherapeutic and transient receptor potential ankyrin 1 (TRPA-1) inhibitor for treatment of triple negative breast cancer |
| Journal | J Control Release |
| Published | 2020 |
| Abstract |
Tumor metastasis is a multistep process, known as metastasis cascade, including primary tumor invading basement membrane, tumor cells infiltrating blood and lymph vessels, circulating, implanting at the distal organ, and forming metastatic nodes. Recently, the role of TRPA-1 in tumor cell proliferation and metastasis has been reported. However, there are few studies on the tumor metastasis inhibition of AP-18. Therefore, researchers first tested the anti-metastasis effect of nanomedicines through wound healing, invasion, and anoikis assays. Then, the possible mechanisms of inhibiting metastasis were further explored in this study.
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| Result | In this study, dual acceptors-targeting and size-switchable DOX and TRPA-1 inhibitor AP-18 co-loaded nanoparticles were formulated for 4T1 solid tumor and metastasis treatment. Compared with tM and MN, tMN achieved the dual advantages of accumulation and penetration in vitro and in vivo. And the core of HA nanogels realized the dual effects of size shrinkage and acquired targeting, which significantly increases the penetration of nanoparticles in tumors. Moreover, DA-tMN exhibited the optimal anti-tumor and anti-metastasis effect synergistically. Furthermore, TRPA-1 inhibition was found to enhance the efficacy of chemotherapy by inhibiting DOX-induced Ca2+ influx and reversing DOX concentration-dependent AKT phosphorylation. In addition, TRPA-1 inhibition was found to regulate EMT-related protein and inhibit the EMT process, which would be a possible cause of tumor metastasis and invasion inhibition. In summary, this study demonstrated chemotherapy DOX combined with TRPA-1 inhibitor AP-18 as a promising strategy for 4T1 solid tumor and metastasis treatment. |
Fig. 2. Schematic illustration of DA-tMN delivered into the tumor. (Wang, 2020)
References
- Bamps, D.; et al. TRP Channel Cooperation for Nociception: Therapeutic Opportunities. Annu Rev Pharmacol Toxicol. 2021, 61: 655-677.
- Wang, Y.; et al. A dual receptors-targeting and size-switchable "cluster bomb" co-loading chemotherapeutic and transient receptor potential ankyrin 1 (TRPA-1) inhibitor for treatment of triple negative breast cancer. J Control Release. 2020, 321: 71-83.
