Digestive physiology of the pig symposium: G protein-coupled receptors in nutrient chemosensation and gastrointestinal hormone secretion.

The gastrointestinal tract is a highly effective and efficient organ system that digests and absorbs nutrients, contributes to the regulation of glucose homeostasis, and signals postprandial satiety. A network of enteroendocrine cells orchestrates these events through the release of neuropeptide hormones secreted in response to the specific nutrient components within the intraluminal milieu. Nutrient chemosensing by these cells is mediated by cell membrane proteins that have been localized to hormone-producing cells. However, functional studies of the nutrient detection abilities of the endocrine cell population have been limited due to its rare and singly distributed cell type. Recent technological advances have enabled investigations with primary endocrine cells that promise to enhance our current understanding of enteroendocrine cell biology. This review focuses on a particular subset of chemosensing receptors, the G protein-coupled receptors (GPCR), that have been identified as putative nutrient sensors of the major macronutrients, lipids, proteins, and carbohydrates by enteroendocrine cells. The contributions of these receptors in directly activating and stimulating hormone secretion in several subsets of enteroendocrine cells will be discussed, based on evidence gathered by functional studies in animal models, in vitro studies in endocrine cell lines, and newly described findings in primary endocrine cells. Key insights in chemosensory detection and hormone secretion from enteroendocrine cells may help further the studies in larger animal models and guide the formulation of feed or supplements to influence the gastrointestinal signals regulating optimal food intake, absorptive capacity, and growth.

Activation of vagal afferents in the rat duodenum by protein digests requires PepT1.

Intestinal infusion of protein digests activates a vago-vagal reflex inhibition of gastric motility. Protein digests release cholecystokinin (CCK) from enteroendocrine cells; however, the precise cellular mechanisms leading to vagal afferent activation is unclear. The hypothesis that the oligopeptide transporter PepT1 plays a major role in the initiation of this vago-vagal reflex was tested by recording activation of duodenal vagal afferent activity and inhibition of gastric motility in response to protein hydrolysates in the presence of 4-aminomethylbenzoic acid (4-AMBA), a competitive inhibitor of PepT1, or 4-aminophenylacetic acid (4-APAA), an inactive 4-AMBA analog. Duodenal infusion of the protein hydrolysate increased vagal afferent discharge and inhibited gastric motility; these responses were abolished by concomitant infusion of 4-AMBA, but not 4-APAA. Duodenal infusion with Cefaclor, a substrate of PepT1, increased duodenal vagal afferent activity; Cefaclor and protein hydrolysates selectively activated CCK-responsive vagal afferents. This study demonstrates that products of protein digestion increase spontaneous activity of CCK-sensitive duodenal vagal afferents via a mechanism involving the oligopeptide transporter PepT1.