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The Role of ATP and Purinergic Receptors in Taste Signaling

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The Pharmacology of Taste

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 275))

Abstract

This review summarizes our understanding of ATP signaling in taste and describes new directions for research. ATP meets all requisite criteria to be considered a neurotransmitter: (1) presence in taste cells, as in all cells; (2) release upon appropriate taste stimulation; (3) binding to cognate purinergic receptors P2X2 and P2X3 on gustatory afferent neurons, and (4) after release, enzymatic degradation to adenosine and other nucleotides by the ectonucleotidase, NTPDase2, expressed on the Type I, glial-like cells in the taste bud. Importantly, double knockout of P2X2 and P2X3 or pharmacological inhibition of P2X3 abolishes transmission of all taste qualities. In Type II taste cells (those that respond to sweet, bitter, or umami stimuli), ATP is released non-vesicularly by a large conductance ion channel composed of CALHM1 and CALHM3, which form a so-called channel synapse at areas of contact with afferent taste nerve fibers. Although ATP release has been detected only from Type II cells, it is also required for the transmission of salty and sour stimuli, which are mediated primarily by the Type III taste cells. The source of the ATP required for Type III cell signaling to afferent fibers is still unclear and is a focus for future experiments. The ionotropic purinergic receptor, P2X3, is widely expressed on many sensory afferents and has been a therapeutic target for treating chronic cough and pain. However, its requirement for taste signaling has complicated efforts at treatment since patients given P2X3 antagonists report substantial disturbances of taste and become non-compliant.

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Acknowledgements

Funding: This work has been supported by grants DC014728 to TEF and DC012555 and DC017679 to S. Kinnamon from the National Institute on Deafness and Other Communication Disorders of NIH.

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Authors and Affiliations

  1. Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, USA

    Sue Kinnamon & Thomas Finger

  2. Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA

    Sue Kinnamon & Thomas Finger

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  1. Sue Kinnamon
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  2. Thomas Finger
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Correspondence to Sue Kinnamon or Thomas Finger .

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  1. Opertech Bio, Inc., Philadelphia, PA, USA

    R. Kyle Palmer

  2. Research and Development, Firmenich, Inc., San Diego, CA, USA

    Guy Servant

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Kinnamon, S., Finger, T. (2021). The Role of ATP and Purinergic Receptors in Taste Signaling. In: Palmer, R.K., Servant, G. (eds) The Pharmacology of Taste . Handbook of Experimental Pharmacology, vol 275. Springer, Cham. https://doi.org/10.1007/164_2021_518

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