GASTROINTESTINAL FUNCTION--SEROTONERGIC CONTROL

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The gastrointestinal tract is controlled by the integration of autonomic nervous system, hormonal, paracrine and neuroendocrine processes. The gut contains a large population of biologically active substances packaged in secretory granules in described "endocrine-paracrine" cells of the mucosa. In mammals, approximately 90% of the content of serotonin is contained in the gastrointestinal tract, predominantly in secretory granules of these "endocrine-paracrine" cells. Serotonin produces marked effects on gastrointestinal function, including effects on gastric acid secretion, motility, gastric emptying and ulcer formation. However, there is a paucity of information available regarding the role of endogenous serotonin to mediate gut function. These studies combine conventional gastric functional methodologies with neuroanatomical, electrophysiological and HLPC techniques to assess the control mechanism of serotonin release into the gastric lumen and portal blood. The functional sequelae of serotonin release on gastric function and its role to mediate gastric emptying of the meal will be determined. The effects of induced hyperplasia of gastric serotonin-secreting cells on gastrointestinal function will be assessed. These studies may provide insight to clinically observed conditions with symptomatology related to hyperplasia of gastrointestinal serotonin. Such conditions include carcinoid syndrome and endocrine cell proliferation subsequent to chronic achlorhydria produced by chronic antiulcer drug therapy or atrophic gastritis.