Neuropods

Abstract

Enteroendocrine cells (EECs) are sensory cells of the gastrointestinal tract. Most EECs reside in the mucosal lining of the stomach or intestine and sense food in the gut lumen. Food signals stimulate the release of hormones into the paracellular space where they either act locally or are taken up into the blood and circulate to distant organs. It recently was recognized that many EECs possess basal processes known as neuropods that not only contain hormones but also connect to nerves. This review describes how neuropods contribute to EEC function beyond typical hormonal actions. For example, gastrointestinal hormones not only act on distant organs, but, through neuropods, some act locally to stimulate other mucosal cells such as intestinal stem cells, enterocytes, or other EECs. With the recent discovery that EECs communicate directly with enteric nerves, EECs not only have the ability to sense food and bacteria in the gastrointestinal tract, but can communicate these signals directly to the nervous system.

Keywords: Enteroendocrine cell; Gut Hormone; Neuron; Neurotransmission; Paracrine.

Figure 1

An enteroendocrine cell neuropod. A confocal microphotograph shows an enteroendocrine cell within the mouse small intestine. An enteroendocrine cell (green) stained with a fluorescently labeled PYY antibody possesses a neuropod that extends below the basal surface of surrounding mucosal cells (eg, enterocytes). Nuclei are stained blue with 4′,6-diamidino-2-phenylindole. Scale bar: 10 μm.

Figure 2

Enteroendocrine cell communication within the gut. A model of an enteroendocrine cell (green) residing in the epithelium of the gut shows that EECs contain both large, dense (blue) and small, clear (yellow) secretory granules that are believed to contain peptide hormones (eg, CCK, PYY, and GLPs) and neurotransmitters (eg, glutamate), respectively. Neurotransmitters are released at synaptic connections with sensory neurons. Peptides such as PYY or GLP-2 are released locally and bind to proliferative cells in the crypt or intestinal subepithelial myofibroblasts, respectively. Peptides (eg, CCK, PYY, and GLPs) also may bind locally to nerves.