title: Calcium-sensing receptor: A new target for therapy of diarrhea.
abstract: Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears "all-inclusive": it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.
authors.affiliation: Sam Xianjun Cheng, Department of Pediatrics, Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Sam Xianjun
authors.initials: SX
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003967:Diarrhea / Q000188:drug therapy* / Q000191:economics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D016527:Drug Costs; D015195:Drug Design; D005769:Gastrointestinal Motility / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000503:physiopathology; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D010539:Permeability; D044169:Receptors, Calcium-Sensing / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000930:Antidiarrheals; C095550:CASR protein, human; C577923:CASR protein, mouse; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled
keywords: Anti-secretory; Cholera toxin; Enteric nervous system; Escherichia coli heat stable toxin; Inflammatory diarrhea; Intestinal barrier function; Intestinal permeability; Oral rehydration solution; Pro-absorptive; Secretory diarrhea