The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands

Dufner, Matthias M.; Kirchhoff, Philipp; Remy, Christine; Hafner, Patricia; Müller, Markus K.; Cheng, Sam X.; Tang, Lieqi; Hebert, Steven C.; Geibel, John P.; Wagner, Carsten A.

doi:10.1152/ajpgi.00571.2004

Cited by 75 publications

(58 citation statements)

References 20 publications

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“…2 C and D). These results provide a molecular basis for protein meal stimulation of gastrin and by logical extension, may account for amino acid stimulation of other CaR-expressing cells, such as acid-secreting parietal cells (17), cholecystokinin-secreting enteroendocrine I cells (28), and insulin-secreting β cells (29).…”

Section: Low Basal Gastrin and Absent Gastrin Response To Luminal Nutmentioning

confidence: 76%

“…CaRs are expressed in rat and human gastric glands on parietal cells, where they regulate acid secretion (17,18). CaRs have also been identified in both rat and human gastric mucus epithelial cells and rat chief cells in primary culture, and this suggests that CaR may regulate mucus and pepsinogen secretion.…”

Section: Deletion Of Car In the Stomach Does Not Alter Oxyntic Glandmentioning

confidence: 98%

“…Parietal cell mass was also unchanged (Fig. S1 Lower), despite parietal cell CaR expression (17,18) and gastrin growth dependence (19).…”

Section: Deletion Of Car In the Stomach Does Not Alter Oxyntic Glandmentioning

confidence: 98%

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Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion

Feng

Petersen²,

Coy³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

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The calcium-sensing receptor (CaR) is the major sensor and regulator of extracellular Ca 2+ , whose activity is allosterically regulated by amino acids and pH. Recently, CaR has been identified in the stomach and intestinal tract, where it has been proposed to function in a non-Ca 2+ homeostatic capacity. Luminal nutrients, such as Ca 2+ and amino acids, have been recognized for decades as potent stimulants for gastrin and acid secretion, although the molecular basis for their recognition remains unknown. The expression of CaR on gastrin-secreting G cells in the stomach and their shared activation by Ca 2+ , amino acids, and elevated pH suggest that CaR may function as the elusive physiologic sensor regulating gastrin and acid secretion. The genetic and pharmacologic studies presented here comparing CaR-null mice and wild-type littermates support this hypothesis. Gavage of Ca 2+ , peptone, phenylalanine, Hepes buffer (pH 7.4), and CaR-specific calcimimetic, cinacalcet, stimulated gastrin and acid secretion, whereas the calcilytic, NPS 2143, inhibited secretion only in the wild-type mouse. Consistent with known growth and developmental functions of CaR, G-cell number was progressively reduced between 30 and 90 d of age by more than 65% in CaR-null mice. These studies of nutrient-regulated G-cell gastrin secretion and growth provide definitive evidence that CaR functions as a physiologically relevant multimodal sensor. Medicinals targeting diseases of Ca 2+ homeostasis should be reviewed for effects outside traditional Ca 2+ -regulating tissues in view of the broader distribution and function of CaR.

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Section: Low Basal Gastrin and Absent Gastrin Response To Luminal Nutmentioning

confidence: 76%

Section: Deletion Of Car In the Stomach Does Not Alter Oxyntic Glandmentioning

confidence: 98%

See 1 more Smart Citation

Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion

Feng

Petersen²,

Coy³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

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show abstract

“…25,31,52 BCECF AM (1 M; Molecular Probes, Invitrogen AG, Basel, Switzerland) was used to monitor pH i . Cells were acidified using the NH 4 Cl (20 mM) prepulse technique, as described previously.…”

Section: Tubule Preparations and Ph I Measurementsmentioning

confidence: 99%

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Renkema¹,

Velić²,

Dijkman³

et al. 2009

Journal of the American Society of Nephrology

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123

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“…In the gastrointestinal tract, CaSR mediates gastric acid and gastrin secretion in human gastric glands and G cells (6,10), and it is also involved in colonic fluid secretion (14). Recently, our current study group, along with others, demonstrated that amino acids induce cholecystokinin (CCK) secretion via CaSR in CCK-producing enteroendocrine cells (17,39).…”

mentioning

confidence: 95%

Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats

Muramatsu

Hira

Mitsunaga

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands

Abstract: The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands.

Cited by 75 publications

References 20 publications

Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion

Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats

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