ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Polymorphisms of CASR gene increase the risk of primary hyperparathyroidism.Journal of endocrinological investigation · 2016Pooled it
- Calcium-Sensing Receptor Regulation of Gastrointestinal Hormone Secretion.Endocrine reviews · 2026Review
- The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut-Brain Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Activation profile of the Atlantic salmon (Salmo salar) calcium-sensing receptor (Casr) by selected L-amino acids.Scientific reports · 2025Article
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- Cellular mechanisms of incretin hormone secretion.Journal of molecular endocrinology · 2024Review
- Sensing of luminal contents and downstream modulation of GI function.JGH open : an open access journal of gastroenterology and hepatology · 2024Review
- Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.Nature metabolism · 2024Article
- Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways.Nature communications · 2023Article
- Temperature sensing by the calcium-sensing receptor.Frontiers in physiology · 2023Article
- Role of the gut-brain axis in energy and glucose metabolism.Experimental & molecular medicine · 2022Review
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- Luminal Chemosensory Cells in the Small Intestine.Nutrients · 2021Review
- Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion.Nutrients · 2021Review
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- First evidence for the presence of amino acid sensing mechanisms in the fish gastrointestinal tract.Scientific reports · 2021Article
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- The Amino Acids Sensing and Utilization in Response to Dietary Aromatic Amino Acid Supplementation in LPS-Induced Inflammation Piglet Model.Frontiers in nutrition · 2021Article
- New Bioactive Peptides Identified from a Tilapia Byproduct Hydrolysate Exerting Effects on DPP-IV Activity and Intestinal Hormones Regulation after Canine Gastrointestinal Simulated Digestion.Molecules (Basel, Switzerland) · 2020Article
10 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 1 country.
Funding
Abstract
The extracellular calcium-sensing receptor (CaSR) has recently been recognized as an L-amino acid sensor and has been implicated in mediating cholecystokinin (CCK) secretion in response to aromatic amino acids. We investigated whether direct detection of L-phenylalanine (L-Phe) by CaSR results in CCK secretion in the native I cell. Fluorescence-activated cell sorting of duodenal I cells from CCK-enhanced green fluorescent protein (eGFP) transgenic mice demonstrated CaSR gene expression. Immunostaining of fixed and fresh duodenal tissue sections confirmed CaSR protein expression. Intracellular calcium fluxes were CaSR dependent, stereoselective for L-Phe over D-Phe, and responsive to type II calcimimetic cinacalcet in CCK-eGFP cells. Additionally, CCK secretion by an isolated I cell population was increased by 30 and 62% in response to L-Phe in the presence of physiological (1.26 mM) and superphysiological (2.5 mM) extracellular calcium concentrations, respectively. While the deletion of CaSR from CCK-eGFP cells did not affect basal CCK secretion, the effect of L-Phe or cinacalcet on intracellular calcium flux was lost. In fact, both secretagogues, as well as superphysiological Ca(2+), evoked an unexpected 20-30% decrease in CCK secretion compared with basal secretion in CaSR(-/-) CCK-eGFP cells. CCK secretion in response to KCl or tryptone was unaffected by the absence of CaSR. The present data suggest that CaSR is required for hormone secretion in the specific response to L-Phe by the native I cell, and that a receptor-mediated mechanism may inhibit hormone secretion in the absence of a fully functional CaSR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.