Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2024; 30(3): 268-279
Published online Jan 21, 2024. doi: 10.3748/wjg.v30.i3.268
Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice
Lie-Qi Tang, Johnathan Fraebel, Shi Jin, Steven P Winesett, Jane Harrell, Wen-Han Chang, Sam Xianjun Cheng
Lie-Qi Tang, Johnathan Fraebel, Shi Jin, Jane Harrell, Department of Pediatrics, University of Florida, Gainesville, FL 32610, United States
Johnathan Fraebel, College of Medicine, University of Florida, Gainesville, FL 32610, United States
Steven P Winesett, Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610, United States
Steven P Winesett, Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, Gainesville, FL 32610, United States
Wen-Han Chang, Department of Medicine, Endocrine Research Unit, Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, United States
Sam Xianjun Cheng, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Florida Shands Children’s Hospital, Gainesville, FL 32608, United States
Author contributions: Cheng SX conceptualized the study; Tang LQ, Fraebel J, and Cheng SX designed the study and analyzed the data; Tang LQ, Fraebel J, Jin S, and Winesett SP performed the experiments; Tang LQ and Cheng SX drafted the manuscript; Harrell J and Chang WH edited the manuscript; Cheng SX finalized the manuscript; and all authors approved the final version of the article.
Supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, No. 1K08HD079674-01 and 1R41HD092133-01; National Institute of Allergy and Infectious Diseases, No. 1A21AI169282; and VA Research Career Scientist Award, No. 1IK6BX004835.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Florida (IACUC Protocol No: 201807567).
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sam Xianjun Cheng, MD, MSc, PhD, Associate Professor, Attending Doctor, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Florida Shands Children’s Hospital, 1600 SW Archer Road, HD 600, Gainesville, FL 32608, United States. sam.cheng@ufl.edu
Received: October 2, 2023
Peer-review started: October 2, 2023
First decision: November 12, 2023
Revised: December 1, 2023
Accepted: January 2, 2024
Article in press: January 2, 2024
Published online: January 21, 2024
Processing time: 107 Days and 16.8 Hours
Core Tip

Core Tip: Treatment of diarrhea remains a global challenge. Enterotoxins induce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Using in vitro models in isolated tissues, we have previously shown that calcium-sensing receptor (CaSR) inhibits both actions. In the present study, we use a mouse model of secretory diarrhea in conjunction with a tissue-specific knockout approach and demonstrate that calcium or calcimimetic via CaSR ameliorates cholera toxin-induced secretory diarrhea in vivo. This study suggests that adding calcium to oral rehydration solution or using calcimimetic to activate intestinal CaSR might represent a new approach for treating secretory diarrheal diseases.