title: The effect of imiquimod on taste bud calcium transients and transmitter secretion.
abstract: 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.
authors.affiliation: Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA. ahuang@siumed.edu.|Center for Integrated Research in Cognitive and Neural Science, Southern Illinois University School of Medicine, Carbondale, IL, USA. ahuang@siumed.edu.
authors.forename: Anthony Y
authors.initials: AY
authors.lastname: Huang
authors.affiliation: Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA.
authors.forename: Sandy Y
authors.initials: SY
authors.lastname: Wu
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism*; D000077271:Imiquimod; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013650:Taste Buds / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D012701:Serotonin; D000255:Adenosine Triphosphate; D000077271:Imiquimod; D002118:Calcium