Endocrine regulation describes the process whereby the sensing cell in the GI tract, an enteroendocrine cell (EEC), responds to a stimulus by secreting a regulatory peptide or hormone that travels via the bloodstream to target cells removed from the point of secretion. Cells responding to a GI hormone express specific receptors for the hormone. Hormones released from the GI tract have effects on cells located in other regions of the GI tract and also on glandular structures associated with the GI tract, such as the pancreas. In addition, GI hormones have effects on other tissues that have no direct role in digestion and absorption, including endocrine cells in liver and brain.
EECs are packed with secretory granules, the products of which are released from the cell in response to chemical and mechanical stimuli to the wall of the GI tract (Fig.
27.5 ). In addition, EECs can be stimulated by neural input or other factors not associated with a meal. The most common EECs in the gut wall are referred to as the “open” type; these cells have an apical membrane that is in contact with the lumen of the GI tract (generally regarded as the location where sensing occurs) and a basolateral membrane through which secretion occurs. There are also “closed”-type EECs that do not have part of their membrane in contact with the luminal surface of the gut; an example is the enterochromaffin-like (ECL) cell in the gastric epithelium, which secretes histamine.
There are many examples of hormones secreted by the GI tract (see
Table 27.1 ); it is worth remembering that the first hormone ever identified was the GI hormone secretin. One of the most well-characterized GI hormones is gastrin, which is released from endocrine cells located in the wall of the distal part of the stomach. Release of gastrin is stimulated by activation of parasympathetic outflow to the GI tract, and gastrin potently stimulates gastric acid secretion in the postprandial period.
•Fig. 27.4 ThethreemechanismsbywhichfunctionintheGItractisregulatedintheintegratedresponsetoameal.
Paracrine regulation describes the process whereby a chemical messenger or regulatory peptide is released from a sensing cell (often an EEC) in the intestinal wall that acts on a nearby target cell by diffusion through the interstitial space. Paracrine agents exert their actions on several different cell types in the wall of the GI tract, including smooth muscle cells, absorptive enterocytes, secretory cells in glands, and even on other EECs. There are several important paracrine agents, and they are listed in
Table 27.1 along with their site of production, site of action, and function. An important paracrine mediator in the gut wall is histamine. In the stomach, histamine is stored and released by ECL cells located in the gastric glands. Histamine diffuses through the interstitial space in the lamina propria to neighboring parietal cells and stimulates production of acid. Serotonin (5-hydroxytryptamine [5-HT]), released from enteric neurons, mucosal mast cells, and specialized EECs called enterochromaffin cells, regulates smooth muscle function and water absorption across the intestinal wall. There are other paracrine mediators in the gut wall, including prostaglandins, adenosine, and nitric oxide (NO); the functions of these mediators are not well described, but they are capable of producing changes in GI function.
Fig. 27.5 Electronmicrographofanopen-typeendocrinecellintheGItract.Notethemicrovilliattheapicalprojectionandthesecretorygranulesinthebasolateralportionofthecell.(FromBarrett
K.
Gastrointestinal Physiology [Lange Physiology Series]. NewYork:McGraw-Hill;2005.)(CourtesyofLeonardR.Johnson,Ph.D.)