Puckering astringent compounds target Gα_q-coupled receptors and induce store-operated calcium entry via Orai channels in the human tongue cell line HSC-3

Astringency is a poorly understood rough sensation in the mouth often experienced in conjunction with bitterness. Despite various theories, the signaling pathways underlying astringency perception remain unclear. We hypothesize that Gα_q-coupled GPCRs are involved in astringency, and store-operated calcium entry (SOCE) may contribute to the lingering perception of astringency by enhancing transient GPCR-mediated Ca2+ signals via Ca2+ influx. Using the human tongue cell line HSC-3 in Ca2+ and cAMP assays (n = 3), we could demonstrate that (I) by applying the Gα_q-specific antagonist FR900359, the astringent compounds epigallocatechin gallate (EGCG) (−104 ± 0.5%, p ≤ 0.0001), tannic acid (TA) (−100 ± 0.4%, p ≤ 0.0001), and rutin (−53 ± 4.0%, p ≤ 0.001) but not the bitter compound quinine (+21 ± 10.0%, ns) activate Gα_q-dependent signaling, and (II) the puckering and lingering astringent EGCG and TA involve SOCE, but not the velvety astringent rutin, suggesting a mechanistic basis for differences in astringent sub-qualities and their persistence as supported by a sensory study (n = 12 trained panelists). Additionally (III), we showed that the astringent compounds and the bitter quinine target Gα_i-coupled GPCRs, like TAS2Rs, a result aligning with sensory studies, as most astringent compounds are perceived as bitter as well. However, the identity of the Gα_q-coupled receptor(s) remains to be determined and represents an important focus for future investigations.