Dataset Information

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

ABSTRACT:

Background and purpose

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.

Experimental approach

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.

Key results

Up to 72% of presynaptic (Type III) taste cells responded to 100 ?M 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.

Conclusion and implications

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.

SUBMITTER: Huang AY

PROVIDER: S-EPMC5056224 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Huang Anthony Y AY Wu Sandy Y SY

British journal of pharmacology 20160906 21

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Taste buds were ...[more]

PMID: 27464850

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Project description:Key pointsTaste transduction occurs in taste buds in the tongue epithelium. The Ca2+ -activated Cl- channels TMEM16A and TMEM16B play relevant physiological roles in several sensory systems. Here, we report that TMEM16A, but not TMEM16B, is expressed in the apical part of taste buds. Large Ca2+ -activated Cl- currents blocked by Ani-9, a selective inhibitor of TMEM16A, are measured in type I taste cells but not in type II or III taste cells. ATP indirectly activates Ca2+ -activated Cl- currents in type I cells through TMEM16A channels. These results indicate that TMEM16A is functional in type I taste cells and contribute to understanding the largely unknown physiological roles of these cells.AbstractThe Ca2+ -activated Cl- channels TMEM16A and TMEM16B have relevant roles in many physiological processes including neuronal excitability and regulation of Cl- homeostasis. Here, we examined the presence of Ca2+ -activated Cl- channels in taste cells of mouse vallate papillae by using immunohistochemistry and electrophysiological recordings. By using immunohistochemistry we showed that only TMEM16A, and not TMEM16B, was expressed in taste bud cells where it largely co-localized with the inwardly rectifying K+ channel KNCJ1 in the apical part of type I cells. By using whole-cell patch-clamp recordings in isolated cells from taste buds, we measured an average current of -1083 pA at -100 mV in 1.5 μm Ca2+ and symmetrical Cl- in type I cells. Ion substitution experiments and blockage by Ani-9, a specific TMEM16A channel blocker, indicated that Ca2+ activated anionic currents through TMEM16A channels. We did not detect any Ca2+ -activated Cl- currents in type II or III taste cells. ATP is released by type II cells in response to various tastants and reaches type I cells where it is hydrolysed by ecto-ATPases. Type I cells also express P2Y purinergic receptors and stimulation of type I cells with extracellular ATP produced large Ca2+ -activated Cl- currents blocked by Ani-9, indicating a possible role of TMEM16A in ATP-mediated signalling. These results provide a definitive demonstration that TMEM16A-mediated currents are functional in type I taste cells and provide a foundation for future studies investigating physiological roles for these often-neglected taste cells.

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

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

Similar Datasets

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