ATP Signaling Is Crucial for Communication from Taste Buds to Gustatory Nerves

Abstract

Taste receptor cells detect chemicals in the oral cavity and transmit this information to taste nerves, but the neurotransmitter(s) have not been identified. We report that adenosine 5'-triphosphate (ATP) is the key neurotransmitter in this system. Genetic elimination of ionotropic purinergic receptors (P2X2 and P2X3) eliminates taste responses in the taste nerves, although the nerves remain responsive to touch, temperature, and menthol. Similarly, P2X-knockout mice show greatly reduced behavioral responses to sweeteners, glutamate, and bitter substances. Finally, stimulation of taste buds in vitro evokes release of ATP. Thus, ATP fulfils the criteria for a neurotransmitter linking taste buds to the nervous system.

ATP release from non-excitable cells

“…Most of these receptors are GPCRs which couple to an increase of [Ca 2+ ] i via the generation of IP 3 . Direct stimulation of G proteins with GTP-γ-S or the G protein activator compound 48/80 strongly suggests that G protein activation is a pre-requisite for agonist-stimulated ATP release [26,41].…”

“…Recent breakthroughs in this field include the role of adenosine triphosphate (ATP) as neurotransmitter and/or modulator in sensory transduction [1][2][3][4][5][6][7][8][9][10], the role of released ATP as a precursor signalling molecule in renal tubulo-glomerular feedback [11,12], the role of released nucleotides for migrating neutrophils [13] and the crucial function of nucleotides in the control of thrombocyte aggregation and haemostasis [14]. The essential features of the purinergic signalling system are well characterised.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…41,42 Type II cells also express voltage-gated sodium and potassium channels that mediate the secretion of ATP as a function of action potential firing rate. 43 Upon secretion, ATP acts as a neurotransmitter on nearby sensory afferent fibers 44,45 ; ATP also acts as a paracrine/autocrine hormone, binding with receptors expressed on neighboring taste receptor cells. [46][47][48][49][50] Type III cells release serotonin, c-amino butyric acid, and norepinephrine and are most notable for possessing synapses.…”

Amino acid variations resulting in functional and nonfunctional zebrafish P2X1 and P2X5.1 receptors

“…Although P2X receptors are widely expressed by both muscle and neural tissue in many organisms, only a handful of functions in these tissues have been attributed to members of this family. Most notably mouse knock outs have implicated P2X 1 in the neurogenic control of smooth muscle [2], P2X 2 and P2X 3 in nociception and as the post-synaptic receptors of neurons that receive input from taste cells [3], and P2X 4 in long-term potentiation [4]. These four examples represent the contribution of only four members of the family, in only a subset of cells known to express P2X receptors.…”