ArticleJCI insight2021
Repurposing calcium-sensing receptor agonist cinacalcet for treatment of CFTR-mediated secretory diarrheas.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Exploring multiple drug actions of a CaNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Cinacalcet Perturbs Membrane Permeability of bEND.3 Endothelial Cells and Suppresses Cell Proliferation.Physiological research · 2025Article
- Zinc inhibits cAMP-induced ClAmerican journal of physiology. Cell physiology · 2025Article
- Targeting the Calcium-Sensing Receptor in Chemically Induced Medium-Grade Colitis in Female BALB/C Mice.Nutrients · 2024Article
- Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration.The ocular surface · 2024Article
- Magnesium for disease treatment and prevention: emerging mechanisms and opportunities.Trends in pharmacological sciences · 2024Review
- Repurposing calcium-sensing receptor activator drug cinacalcet for ADPKD treatment.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Calcium/calcimimeticWorld journal of gastroenterology · 2024Article
- Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.The Journal of clinical investigation · 2024Article
- Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.Pharmaceutics · 2024Review
- Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Ca2+ fortified oral rehydration solution is effective in reducing diarrhea morbidity in cholera toxin-pretreated mice.Research square · 2023Article
- Ocular Surface Ion Transport and Dry Eye Disease.Current ophthalmology reports · 2022Article
- Lubiprostone is non-selective activator of cAMP-gated ion channels and Clc-2 has a minor role in its prosecretory effect in intestinal epithelial cells.Molecular pharmacology · 2022Article
- SLC26A6-selective inhibitor identified in a small-molecule screen blocks fluid absorption in small intestine.JCI insight · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Diarrhea is a major cause of global mortality, and outbreaks of secretory diarrhea such as cholera remain an important problem in the developing world. Current treatment of secretory diarrhea primarily involves supportive measures, such as fluid replacement. The calcium-sensing receptor (CaSR) regulates multiple biological activities in response to changes in extracellular Ca2+. The FDA-approved drug cinacalcet is an allosteric activator of CaSR used for treatment of hyperparathyroidism. Here, we found by short-circuit current measurements in human colonic T84 cells that CaSR activation by cinacalcet reduced forskolin-induced Cl- secretion by greater than 80%. Cinacalcet also reduced Cl- secretion induced by cholera toxin, heat-stable E. coli enterotoxin, and vasoactive intestinal peptide (VIP). The cinacalcet effect primarily involved indirect inhibition of cystic fibrosis transmembrane conductance regulator-mediated (CFTR-mediated) Cl- secretion following activation of CaSR and downstream phospholipase C and phosphodiesterases. In mice, cinacalcet reduced fluid accumulation by more than 60% in intestinal closed loop models of cholera and traveler's diarrhea. The cinacalcet effect involved both inhibition of CFTR-mediated secretion and stimulation of sodium-hydrogen exchanger 3-mediated absorption. These findings support the therapeutic utility of the safe and commonly used drug cinacalcet in CFTR-dependent secretory diarrheas, including cholera, traveler's diarrhea, and VIPoma.
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Registered trials
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.