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Atrial natriuretic peptides are a family of natriuretic peptides synthesized primarily in the atria of the heart but recent evidence suggests their synthesis and potential role in the gastrointestinal tract. Within in the stomach, atrial natriuretic peptide (ANP) prohormone gene expression has been localized in the rat gastric antrum using immunohistochemistry and in situ hybridization to mucosal cells in the lower portion of the antropyloric glands. Co-localization with serotonin in these cells indicates these cells are enterochromaffin cells. Fasting for 72 hours in adult rats produces a significant (P<0.05) decrease in the levels of ANP prohormone mRNA and its gene products proANP 1-30, (i.e., long acting natriuretic peptide) and ANP to approximately 33% of that of fed rats. Food intake, on the other hand, increases atrial natriuretic peptides within the circulation approximately 45%. These findings taken together suggest that distension or stretch of the stomach by food may be an important physiologic regulator of the natriuretic peptide system within the GI tract similar to stretch of the heart being important for regulation of the same gene within the heart. The secretion of ANP from the antrum of the stomach appears to be regulated by both cholingeric (decrease ANP secretion) and non-cholingeric (increase ANP secretion) intramural neurons. Since atrial natriuretic peptides are present within the small intestine and colon, as well as the stomach, as food moves through the small intestine and colon and, thereby, stretches the small intestine and colon this may 1) stimulate ANP prohormone gene expression and/or 2) enhance release of its gene products to assist in the coordination and fluid homeostasis and motility throughout the GI tract. Transcripts for natriuretic peptide receptor subtypes NPR-A, NPR-B and NPR-C are present in both mucosa and muscle tissues of the antrum of the stomach. ANP, brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) stimulate the production of cGMP in antral mucosa and bind to these receptors in vitro with a potency of ANP>BNP>CNP suggesting that these receptors are functional. The fact that atrial natriuretic peptides are localized near the basolateral surface of the enterochromaffin cells also suggests a mechanism for the observation that ANP increases in the circulation secondary to food intake. This basolateral plasma membrane is juxtaposed to capillaries via which atrial peptides could enter the circulation from the stomach. Thus, in addition to helping control fluid homeostasis within the gastrointestinal tract, the release of these peptides from the stomach into the circulation after a meal suggests that the peptides synthesized within the stomach may also contribute to overall fluid homeostasis of the body by their ability to enhance sodium and water excretion via the kidney.