Extra-Oral Taste Receptors-Function, Disease, and Perspectives

Abstract

Taste perception is crucial for the critical evaluation of food constituents in human and other vertebrates. The five basic taste qualities salty, sour, sweet, umami (in humans mainly the taste of L-glutamic acid) and bitter provide important information on the energy content, the concentration of electrolytes and the presence of potentially harmful components in food items. Detection of the various taste stimuli is facilitated by specialized receptor proteins that are expressed in taste buds distributed on the tongue and the oral cavity. Whereas, salty and sour receptors represent ion channels, the receptors for sweet, umami and bitter belong to the G protein-coupled receptor superfamily. In particular, the G protein-coupled taste receptors have been located in a growing number of tissues outside the oral cavity, where they mediate important processes. This article will provide a brief introduction into the human taste perception, the corresponding receptive molecules and their signal transduction. Then, we will focus on taste receptors in the gastrointestinal tract, which participate in a variety of processes including the regulation of metabolic functions, hunger/satiety regulation as well as in digestion and pathogen defense reactions. These important non-gustatory functions suggest that complex selective forces have contributed to shape taste receptors during evolution.

Keywords: gastrointestinal tract; metabolism and endocrinology; nutrient sensing; pathogen defense; taste receptors.

Figure 1

Cell types involved in the detection of taste stimuli. Shown are schematic drawings of type II taste receptor cells (left), enteroendocrine cells of the GI tract (middle) and brush cells (right). The signal components involved/implied in signal transduction are depicted: Adenosine triphosphate (ATP), calcium ions (Ca²⁺), Calcium homeostasis modulator 1 and 3 (CALHM1/3), G protein-coupled receptor (GPCR), G protein alpha subunit α-gustducin (Gαgust), G protein beta subunit (Gβ), G protein gamma subunit (Gγ), Inositol 1,4,5-trisphosphate (IP₃), Phospholipase C beta 2 (PLCβ2), sodium ions (Na⁺), transient receptor potential cation channel subfamily M members 4 and 5 (TRPM5/4).

Figure 2

Molecules and organisms implicated in triggering GPCR-mediated defense reactions in non-gustatory epithelia. Gastrointestinal infections with succinate secreting helminths and bacteria secreting quorum-sensing molecules (homoserine lactones, e.g., C6-HSL) or metabolites (e.g., 2-butanone) are believed to result in the activation of GPCRs including bitter taste receptors. A ribbon structure (seen from the top) of a homology model of human bitter taste receptor TAS2R14 [derived from (49), modified with Maestro 12.9 software (Schrodinger)], one of the TAS2Rs implicated in innate immune responses, is depicted at the bottom.