TRPV Assays
Background of TRPV
TRPVs, activated by vanillin, vanillic acid, and capsaicin in the plants, are thermo-TRP channels, such as TRPV1, TRPV2, TRPV3, and TRPV4 can be activated by heat. There are six different members (TRPV1-6) in this family. Compared to TRPV1-4 which are referred to as nociceptors that sense the damaging signals, TRPV5 and TRPV6 are epithelial calcium ion channels.
Fig. 1. Structure of transient receptor potential vanilloid 1 (TRPV1). (Bamps, 2021)
Subtypes and Mechanisms of TRPV
TRPV1 was first identified and cloned in the late 1990s. It can be activated by multiple stimuli, such as moderate heat (43℃), low pH, capsaicin, ethanol, endogenous lipids, black pepper, and garlic as well as inflammatory mediators. TRPV1 is expressed in most neurons and is widely investigated. In nerve injury associated with neuropathic pain and chronic pain, TRPV1 plays a central role.
- TRPV2
TRPV2 shares 50% of sequence homology with TRPV1 and is activated by higher temperatures (52℃). Other stimuli responsible for TRPV2 activation include osmotic stress and mechanical stretch. TRPV2 is expressed both in neuronal and nonneuronal cells. However, the exact physiological function of this TRPV member remains to be clarified.
TRPV3 is expressed in the brain, spinal cord, trigeminal ganglia, and DRG neurons. It acts as a thermo-sensor in the skin and is activated by temperatures higher than 34℃. Other activators of TRPV3 include endogenous ligands such as PGE2, ATP, bradykinin, and histamine.
TRPV4 is a nonselective cation channel and is activated by temperatures higher than 27℃, mechanical stimuli, hypotonicity, and metabolites of arachidonic acid. It serves as a sensor of osmolality and mechanical stretch.
- TRPV5
TRPV5 is mainly expressed in kidney epithelial cells and plays an important role in the reabsorption of Ca2+. It can be regulated by various factors, including 1,25-dihydroxyvitamin D3, parathyroid hormone, dietary Ca2+, and acid-base status change of pH.
TRPV6 shares some common features with TRPV5. They are co-expressed in several tissues, such as the intestine, kidney, prostate, and testis. Unlike TRPV1-4, they are selective channels for Ca2+. The gene expression of TRPV6 is upregulated in most common cancers, including prostate and breast cancers. TRPV6 is also an important channel for male fertility.
Assay List of TRPV Channels
Creative Biolabs can provide a range of assays of TRPV channels. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Novel insights into the TRPV3-mediated itch in atopic dermatitis |
| Journal | J Allergy Clin Immunol |
| Published | 2021 |
| Abstract | Chronic pruritus (itch) is a widespread and debilitating condition, associated with dermatological, systemic, neuropathic, or psychogenic disorders. Heat-induced activation of TRPV3 stimulates the release of a potent itch-inducer, thymic stromal lymphopoietin (TSLP), from cultured murine KCs. In mice, intradermal injection of carvacrol, a TRPV3 agonist, elicits scratching behaviors. Gain-of-function mutations in TRPV3 have been confirmed in Olmsted Syndrome, a rare pruritic genodermatosis in humans, and induce atopic dermatitis (AD)-like inflammation in rodents. TRPV3 is upregulated in the skin of patients with AD. Despite this, much remains unknown about the clinical relevance of TRPV3-linked pathways in human dermatitis and pruritus. This study discovered a novel neuro-epidermal BNP-TRPV3-Serpin E1-mediated pathway in severe AD. Serpin E1 was identified as a new itch-inducer. The study proposes this pathway represents an important target for the treatment of AD. |
| Result |
This study provides a clear link between TRPV3 and dermatitis. In AD conditions, IL-31 induces BNP synthesis and release from sensory neurons. BNP subsequently binds to NPR1 on KCs to upregulate TRPV3 transcripts. This could increase the surface expression of TRPV3, resulting in heightened TRPV3 activity and increased Serpin E1 release. Serpin E1 activates sensory fibers in the skin and promotes itch transduction. This study reveals a disease-relevant neuro-epidermal pathway for TRPV3 upregulation and sensitization. It also highlights the role of TRPV3-linked mediators in human dermatitis and pruritus, with Serpin E1 representing a novel itch-inducer. Based on these results, targeting TRPV3 signaling will prove beneficial for the treatment of chronic itch conditions.
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Fig. 2. A model for TRPV3-mediated itch and sensitization in AD. (Larkin, 2021)
References
- Bamps, D.; et al. TRP Channel Cooperation for Nociception: Therapeutic Opportunities. Annu Rev Pharmacol Toxicol. 2021, 61: 655-677.
- Larkin, C.; et al. Novel insights into the TRPV3-mediated itch in atopic dermatitis. J Allergy Clin Immunol. 2021, 147(3): 1110-1114 e5.
