A model for integrative study of human gastric acid secretion.
We have developed a unique virtual human model of gastric acid secretion and its regulation in which food provides a driving force. Food stimulus triggers neural activity in central and enteric nervous systems and G cells to release gastrin, a critical stimulatory hormone. Gastrin stimulates enterochromaffin-like cells to release histamine, which, together with acetylcholine, stimulates acid secretion from parietal cells. Secretion of somatostatin from antral and corpus D cells comprises a negative-feedback loop. We demonstrate that although acid levels are most sensitive to food and nervous system inputs, somatostatin-associated interactions are also important in governing acidity. The importance of gastrin in acid secretion is greatest at the level of transport between the antral and corpus regions. Our model can be applied to study conditions that are not yet experimentally reproducible. For example, we are able to preferentially deplete antral or corpus somatostatin. Depletion of antral somatostatin exhibits a more significant elevation of acid release than depletion of corpus somatostatin. This increase in acid release is likely due to elevated gastrin levels. Prolonged hypergastrinemia has significant effects in the long term (5 days) by promoting enterochromaffin-like cell overgrowth. Our results may be useful in the design of therapeutic strategies for acid secretory dysfunctions such as hyper- and hypochlorhydria.
Joseph
Ian M P
IM
Departments of Microbiology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Zavros
Yana
Y
Merchant
Juanita L
JL
Kirschner
Denise
D
D002455:Cell Division / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology; D004435:Eating / Q000502:physiology; D004759:Enterochromaffin Cells / Q000166:cytology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D011706:Pyloric Antrum / Q000378:metabolism; D013004:Somatostatin / Q000172:deficiency
D005755:Gastrins; D013004:Somatostatin