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Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor
- Source :
- J Mol Endocrinol
- Publication Year :
- 2020
- Publisher :
- Bioscientifica, 2020.
-
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-α (PPAR-α) 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-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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
medicine.drug_class
Fluorescent Antibody Technique
030209 endocrinology & metabolism
Sodium Chloride
digestive system
Article
Cell Line
03 medical and health sciences
0302 clinical medicine
Endocrinology
Dopamine receptor D1
Fenofibrate
Cell Line, Tumor
Internal medicine
Gastrins
Pyloric Antrum
medicine
Humans
Gastrin-Secreting Cells
PPAR alpha
Secretion
RNA, Messenger
Phytohemagglutinins
Receptor
Molecular Biology
Cells, Cultured
Gastrin
Ovarian Neoplasms
Chemistry
Receptors, Dopamine D1
digestive, oral, and skin physiology
Receptor antagonist
Immunohistochemistry
030104 developmental biology
Renal sodium excretion
Cholecystokinin B receptor
Female
G cell
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 14796813 and 09525041
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....8f07c34c890320fb743a0296555d5241