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Stomach Gastrin is Regulated by Sodium via PPAR-α and Dopamine D1 Receptor.

07:00 EST 1st December 2019 | BioPortfolio

Summary of "Stomach Gastrin is Regulated by Sodium via PPAR-α and Dopamine D1 Receptor."

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known, how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested these hypotheses: 1) a sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion; and 2) dopamine, via the D1R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist, FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D1-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells, via the D1R, because the D5R, the other D1-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate, acutely, an oral sodium load. Dopamine, via the D1R, by interacting with PPAR-α, is involved in this process.

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This article was published in the following journal.

Name: Journal of molecular endocrinology
ISSN: 1479-6813
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Endocrine cells which secrete GASTRIN, a peptide that induces GASTRIC ACID secretion. They are found predominantly in the GASTRIC GLANDS of PYLORIC ANTRUM in the STOMACH, but can also be found in the DUODENUM, nervous and other tissues.

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L-Tryptophyl-L-methionyl-L-aspartyl-L-phenylalaninamide. The C-terminal tetrapeptide of gastrin. It is the smallest peptide fragment of gastrin which has the same physiological and pharmacological activity as gastrin.

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