Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.
CFTR
Cholera
Drug repurposing
Traveler's diarrhea
VIPoma
Journal
Translational research : the journal of laboratory and clinical medicine
ISSN: 1878-1810
Titre abrégé: Transl Res
Pays: United States
ID NLM: 101280339
Informations de publication
Date de publication:
09 Sep 2023
09 Sep 2023
Historique:
received:
12
01
2023
revised:
24
07
2023
accepted:
01
09
2023
pubmed:
8
9
2023
medline:
8
9
2023
entrez:
7
9
2023
Statut:
aheadofprint
Résumé
Cyclic nucleotide elevation in intestinal epithelial cells is the key pathology causing intestinal fluid loss in secretory diarrheas such as cholera. Current secretory diarrhea treatment is primarily supportive, and oral rehydration solution is the mainstay of cholera treatment. There is an unmet need for safe, simple and effective diarrhea treatments. By promoting cAMP hydrolysis, extracellular calcium-sensing receptor (CaSR) is a regulator of intestinal fluid transport. We studied the antidiarrheal mechanisms of FDA-approved CaSR activator cinacalcet and tested its efficacy in clinically relevant human cell, mouse and intestinal organoid models of secretory diarrhea. By using selective inhibitors, we found that cAMP agonists-induced secretory short-circuit currents (I
Identifiants
pubmed: 37678755
pii: S1931-5244(23)00141-X
doi: 10.1016/j.trsl.2023.09.001
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.