Immunoelectron microscopy revealed that peripheral afferent nerve fibers innervating taste buds contain calcitonin gene-related peptide (CGRP), which may be as an efferent transmitter released from peripheral axon terminals. In this report, we determined the targets of CGRP within taste buds and studied what effect CGRP exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura-2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings showed that a subset of Presynaptic (Type III)

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.

Combined with the recent findings that GABA depresses taste-evoked ATP secretion, the current results indicate that SP elicited secretion of GABA, which provided negative feedback onto Type II (receptor) cells to reduce taste-evoked ATP secretion. These findings are consistent with a role for SP as an inhibitory transmitter that shapes the peripheral taste signals, via GABAergic signalling, during the processing of gustatory information in taste buds. Notably, the results suggest that SP is intimately associated with GABA in mammalian taste signal processing and demonstrate an unanticipated route for sensory information flow within the taste bud.

Considering that nutrients are required in health and diseases, the detection and ingestion of food to meet the requirements is attributable to the sense of taste. Altered taste sensations lead to a decreased appetite, which is usually one of the frequent causes of malnutrition in patients with diseases. Ongoing taste research has identified a variety of drug pathways that cause changes in taste perceptions in cancer, increasing our understanding of taste disturbances attributable to aberrant mechanisms of taste sensation. The evidence discussed in this review, which addresses the implications of innate immune responses in the modulation of taste functions, focuses on the adverse effects on taste transmission from taste buds by immune modulators responsible for alterations in the perceived intensity of some taste modalities. Another factor, damage to taste progenitor cells that directly results in local effects on taste buds, must also be considered in relation to taste disturbances in patients with cancer. Recent discoveries discussed have provided new insights into the pathophysiology of taste dysfunctions associated with the specific treatments. SIGNIFICANCE STATEMENT The paradigm that taste signals transmitted to the brain are determined only by tastant-mediated activation via taste receptors has been challenged by the immune modification of taste transmission through drugs during the processing of gustatory information in taste buds. This article reports the findings in a model system (mouse taste buds) that explain the basis for the taste dysfunctions in patients with cancer that has long been observed but never understood.