The effect of imiquimod on taste bud calcium transients and transmitter secretion

Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to the brain. Here, we tested the underlying assumption that imiquimod modifies taste transmitter secretion in taste buds of mice.

Taste buds were isolated from C57BL/6J mice. The effects of imiquimod on transmitter release in taste buds were measured using calcium imaging with cellular biosensors, and examining the net effect of imiquimod on taste-evoked ATP secretion from mouse taste buds.

Up to 72% of presynaptic (Type III) taste cells responded to 100 μM imiquimod with an increase in intracellular Ca²⁺ concentrations. These Ca²⁺ responses were inhibited by thapsigargin, an inhibitor of the sarco/endoplasmic reticulum Ca²⁺ -ATPase, and by U73122, a PLC inhibitor, suggesting that the Ca²⁺ mobilization elicited by imiquimod was dependent on release from internal Ca²⁺ stores. Moreover, combining studies of Ca²⁺ imaging with cellular biosensors showed that imiquimod evoked secretion of 5-HT, which then provided negative feedback onto receptor (Type II) cells to reduce taste-evoked ATP secretion.

Our results provide evidence that there is a subset of taste cells equipped with a range of intracellular mechanisms that respond to imiquimod. The findings are also consistent with a role of imiquimod as an immune response modifier, which shapes peripheral taste responses via 5-HT signalling.