Our senses help us perceive the external environment and respond appropriately to external cues. Many of our senses, including our sense of taste, use G-protein coupled receptors (GPCRs) for transduction of environmental signals. Taste sensation is mediated through two families of related, evolutionarily conserved GPCRs known as T1Rs and T2Rs, originally described within taste buds of the tongue.1 Through these basic elements, we are able to generate a diverse repertoire of taste sensations including sweet, bitter and savoury (umami) tastes. For example, sweet taste sensation is initiated by ligand binding to the extracellular domain of the heterodimeric receptor complex formed by the GPCRs T1R2 and T1R3, whereas savoury taste sensation is initiated through a heterodimer of T1R1 and T1R3.1 The activated intracellular domain of the heterodimeric receptor complex then couples with a specific G protein alpha subunit, G alpha gustducin, resulting in downstream effector signals including increased intracellular calcium.2 The activity of G alpha gustducin also leads to activation of transient receptor potential ion channel 5 (TRPM5), a cation channel whose downstream effects are not yet well understood.3

The discovery of G alpha gustducin expression in luminal gut epithelium raised the intriguing possibility that the gut is somehow able to “taste” luminal contents.4 More recently, taste receptors and their downstream effectors were shown to be expressed within the stomach, proximal …