The Role of Neuropeptides in Peripheral Taste Signaling

Chemesthesis, the general chemical sensitivity of the skin and mucus membranes in the oronasal cavities and being perceived as pungency, irritation or heat, impacts taste responsiveness. The modulation of taste nerve responses is thought to be produced indirectly, via stimulation of peripheral sensory nerve terminals that have ability to release stored transmitters, e.g., calcitonin gene‐related peptide (CGRP) and substance P (SP), onto taste cells implying playing a role in gustatory signaling, by the functions of somatosensory neurons. The underlying assumption has been that neuropeptides exert their effects on taste transmitter secretion in taste buds of mice, a well‐accepted model for studying taste bud functions, as theoretically may relate to the processing of the gustatory information. Indeed, CGRP shapes peripheral taste signals via serotonergic signaling. In this study, using a combination of Ca 2+ imaging with cellular biosensors – genetically‐engineered Chinese Hamster Ovary (CHO) cells, transgenic mice expressing green fluorescent protein (GFP) in the specific taste cell type and immunostaining, we showed that the net effect of SP reduced taste‐evoked ATP secretion from mouse taste buds. Specifically, SP elicited phospholipase C (PLC) activation‐dependent intracellular Ca 2+ transients in taste cells via neurokinin 1 (NK1) receptors, most likely on glutamate‐aspartate transporter (GLAST)‐expressing Type I cells. Recently, γ‐aminobutyric acid (GABA) as well as the associated synthetic enzyme have been identified in Type I cells. Consequently, Type I cells secrete GABA in respond to SP. Combined with the recent findings that GABA provides negative paracrine feedback onto Receptor (Type II) cells by activating GABA A and/or GABA B receptors and reducing taste‐evoked ATP secretion, our results showed that taste‐evoked ATP secretion from intact taste buds, which remain cell‐cell communication intact, was reduced when SP was co‐applied with taste stimuli in the bath medium. We conclude that SP plays a role as an inhibitory transmitter that shapes peripheral taste signals via GABAergic signaling during processing gustatory information in taste buds. This seemingly tangled complex represents a new concept of taste signaling and that neuropeptides released from afferent sensory terminals play a regulatory role in processing taste signals. Support or Funding Information AAA Fellows Grant Award Program Research Seed Grant to AYH (AAA‐3419). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .