# TRPV2 and TRPC5 are potential targets for astringent phytochemicals

## TL;DR

This study shows that TRPV2 and TRPC5 ion channels are affected by astringent compounds, which may influence oral sensations and health.

## Contribution

The study identifies TRPV2 and TRPC5 as novel targets for astringent phytochemicals and reveals species-specific effects.

## Key findings

- Astringent compounds like oxi-EGCG and tannic acid modulate TRPV2 and TRPC5 channels differently in rats and humans.
- Genistein potentiates TRPV2 and TRPC5, while genistin does not.
- TRPV2 and TRPC5 can interact with mucin 1, a protein in the oral environment.

## Abstract

Astringency is a multimodal sensory experience resulting from complex interactions between chemical compounds and the oral environment, involving tactile, chemosensory and thermosensory pathways. Recent human studies have examined the role of the polymodal transient receptor potential (TRP) channels TRPV1 and TRPA1 in astringency perception; however, other thermo- and mechanosensitive TRP channels expressed in oral epithelial cells and in trigeminal neurons innervating the mouth and tongue may also contribute to this complex sensation. This study explored the effects of structurally distinct representatives of astringent compounds on TRPV2 and TRPC5 channels. Using patch-clamp electrophysiology, microfluorimetry, molecular modeling, and mutagenesis, we show that the auto-oxidation products of the most abundant green tea polyphenol (−)-epigallocatechin-3-gallate (oxi-EGCG) significantly increase the activation of rat TRPV2 while blocking the human orthologue. The plant-derived isoflavone genistein, but not its glycoside form genistin, potentiated human TRPV2 and sensitized TRPC5-mediated currents activated by depolarizing voltage and the alpha subunit of G-proteins. Tannic acid, another astringent substance, potentiated rat TRPV2 and inhibited human TRPV2 and TRPC5. Furthermore, we show that both channels can interact with mucin 1, a transmembrane glycoprotein present in the native oral environment. Our data also provide the first evidence of heat-induced activation of human TRPV2. Considering previous evidence for TRPV2 and TRPC5 expression in the oral cavity and their roles in oral pain and cancer, our findings indicate that these polymodal channels may participate not only in detecting specific astringent compounds, but also in mediating their broader health-related and anesthetic actions.

Image 1

•TRPV2 and TRPC5 ion channels are modulated by different types of astringents.•Astringents exhibit different effects on rat and human TRPV2 orthologues.•Genistein, but not its glycoside form genistin, potentiates TRPV2 and TRPC5.•Both channels can interact with the transmembrane glycoprotein mucin 1.

TRPV2 and TRPC5 ion channels are modulated by different types of astringents.

Astringents exhibit different effects on rat and human TRPV2 orthologues.

Genistein, but not its glycoside form genistin, potentiates TRPV2 and TRPC5.

Both channels can interact with the transmembrane glycoprotein mucin 1.