Enteroendocrine cells: a site of 'taste' in gastrointestinal chemosensing

Abstract

Purpose of review: This review discusses the role of enteroendocrine cells of the gastrointestinal tract as chemoreceptors that sense lumen contents and induce changes in gastrointestinal function and food intake through the release of signaling substances acting on a variety of targets locally or at a distance.

Recent findings: Recent evidence supports the concept that chemosensing in the gut involves G protein-coupled receptors and effectors that are known to mediate gustatory signals in the oral cavity. These include sweet-taste and bitter-taste receptors, and their associated G proteins, which are expressed in the gastrointestinal mucosa, including selected populations of enteroendocrine cells. In addition, taste receptor agonists elicit a secretory response in enteroendocrine cells in vitro and in animals in vivo, and induce neuronal activation.

Summary: Taste-signaling molecules expressed in the gastrointestinal mucosa might participate in the functional detection of nutrients and harmful substances in the lumen and prepare the gut to absorb them or initiate a protective response. They might also participate in the control of food intake through the activation of gut-brain neural pathways. These findings provide a new dimension to unraveling the regulatory circuits initiated by luminal contents of the gastrointestinal tract.

Figure 1. Possible pathways involved in nutrient sensing by enteroendocrine cells

Putative sites of chemosensing are localized on the cell surface. When the luminal content (nutrients and non-nutrients) comes in contact with enteroendocrine cells, it induces release of hormones that enter blood vessels or signaling molecules that activate extrinsic or intrinsic afferent neurons thereby sending neuronal messages to the central nervous system and to enteric neurons. Released molecules can also act directly on adjacent cells, including other enteroendocrine cells and other types of epithelial cells like brush cells.

Figure 2. Postulated mechanism involving sweet (T1R) and bitter (T2R) taste receptors on enteroendocrine cells

Taste receptors couple to G proteins upon activation to induce intracellular Ca²⁺ increase resulting in release of peptides, which regulate a variety of gastrointestinal functions, including action on organs associated with the gut like the gallbladder and pancreas, via neuronal or humoral pathways to induce digestion and absorption or protection from harmful substances. Released peptides can also control food intake through the gut–brain axis.