The Pharmacology and Signaling of Bitter, Sweet, and Umami Taste Sensing

The taste cell signaling model. Tastant molecules, acting as agonist ligands, bind to and stabilize the active conformation of GPCRs in the apical microvilli of type II taste cells. The active receptor interacts with gustducin and other G proteins that consequently release their βγ subunits to stimulate PLCβ₂. Hydrolysis of membrane PIP₂ by PLCβ₂ generates inositol trisphosphate (IP₃) that, in turn, interacts with and opens the IP₃R3 channel on internal calcium stores. The increase in [Ca²⁺]_i activates TRPM5-mediated changes in membrane potential (ΔV), and subsequently ATP is released through the pannexin-1 hemichannel. Secreted ATP acts on P2Y purinergic receptors on type III taste cells, causing the exocytotic release of 5-HT into the synapse between type III cells and afferent sensory neurons. ATP from type II cells is also believed to stimulate afferent sensory neurons. Model diagrammed according to (128, 133) and Stephen Roper, personal communications.