Amino acid sensing in the gastrointestinal tract

Ana San Gabriel, Hisayuki Uneyama

Rapid progress in gastroenterology during the first part of the last century has shown that gastrointestinal (GI) function is regulated by neuroendocrine, paracrine and endocrine signals. However, recent advances in chemical sensing, especially in the last decade, have revealed that free L-amino acids (AA), among other nutrients, play a critical role in modifying exocrine and endocrine secretion, modulating protein digestion, metabolism and nutrient utilization, and supporting the integrity and defense of the GI mucosa. Many of the mechanisms by which AAs elicit these functions in the GI has been linked to the traditional concept of hormone release and nervous system activation. But most these effects are not direct. AAs appear to function by binding to a chemical communication system such as G protein-coupled receptors (GPCRs) that activate signaling pathways. These intracellular signals, although their molecular bases are not completely elucidated yet, are the ones responsible for the neuronal activity and release of hormones that in turn regulate GI functions. This review aims to describe the distribution of the known GPCRs from the class 3 superfamily that bind to different kinds of AA, especially from the oropharyngeal cavity to the stomach, what kind of taste qualities they elicit, such as umami, bitter or sweet, and their activity in the GI tract.