Figure 9.

Proposed signalling pathway of the influence of denatonium on transepithelial ion transport. Denatonium binding to Tas2R in brush cells leads to a G_βγ-dependent activation of PLC_β2, which results in an activation of IP3 receptors. The increase in [Ca²⁺]_i leads to an activation of Trpm5 followed by a release of ACh. The released ACh then binds to nAChR on neighbouring cells, resulting in an inhibition of ENaC and chloride channels. Simultaneously, the G_α-dependent reduction of [cAMP]_i in brush cells might lead to an additional decrease in ENaC, CFTR, and KCNQ1 as well as NKCC1 activity.