Figure 1.

Taste sensation signaling and glucagon-like peptide 1 (GLP-1). Legend: A sugar molecule binds to heterodimeric G protein coupled receptor (GPCR) that consists of taste receptor type 1 member 2 (TAS1R2) and taste receptor type 1 member 3 (TAS1R3). Downstream signaling ultimately leads to release of ATP. Specifically, upon PLCβ2 activation IP3 as a second messenger is generated. IP3 releases intracellular Ca²⁺. Released Ca²⁺ gates transient receptor potential cation channel subfamily M member 5 (TRPM5), which results in cellular depolarization. The generated action potentials cause a release of ATP through voltage-gated calcium homeostasis modulator 1 (CALMH1) that engages purinergic receptors for ATP on the sensory nerve fibers. Sensory nerve fibers convey information to higher order neurons in the Nucleus Tractus Solitarus (NTS). Adenosine triphosphate (ATP) as a transmitter represents the major line of communication from TBC type II cells to the brain. In addition, when stimulated with sweet molecules, glucagon like peptide -1 (GLP-1) is also immediately released from TBCs by vesicular mechanisms. GLP-1 activates GLP-1 receptor (GLP-1 R) on the adjacent gustatory nerves. It seems that GLP-1 acts as ancillary neurotransmitter in cooperation with ATP for maximal activation of nerve fibers that transmit gustatory code for the perception of sweet.