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Stomach gastrin is regulated by sodium via PPAR-? and dopamine D1 receptor.


ABSTRACT: 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-? (PPAR-?) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested the following hypotheses: (1.) the 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-?, 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-? agonist FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-? 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-?, is involved in this process.

SUBMITTER: Xu P 

PROVIDER: S-EPMC7654719 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor.

Xu Peng P   Gildea John J JJ   Zhang Chi C   Konkalmatt Prasad P   Cuevas Santiago S   Bigler Wang Dora D   Tran Hanh T HT   Jose Pedro A PA   Felder Robin A RA  

Journal of molecular endocrinology 20200201 2


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 the foll  ...[more]

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