title: The role of the calcium-sensing receptor in gastrointestinal inflammation.
abstract: The gastrointestinal (GI) tract must balance the extraction of energy and metabolic end-products from ingested nutrition and resident gut microbes and the maintenance of a symbiotic relationship with this microbiota, with the ability to mount functional immune responses to pathogenic organisms to maintain GI health. The gut epithelium is equipped with bacteria-sensing mechanisms that discriminate between pathogenic and commensal microorganisms and regulate host responses between immunity and tolerance. The epithelium also expresses numerous nutrient-sensing receptors, but their importance in the preservation of the gut microbiota and immune homeostasis remains largely unexplored. Observations that a deficiency in the extracellular calcium-sensing receptor (CaSR) using intestinal epithelium-specific receptor knockout mice resulted in diminished intestinal barrier integrity, altered composition of the gut microbiota, modified expression of intestinal pattern recognition receptors, and a skewing of local and systemic innate responses from regulatory to stimulatory, may change the way that this receptor is considered as a potential immunotherapeutic target in gut homeostasis. These findings suggest that pharmacologic CaSR activators and CaSR-based nutrients such as calcium, polyamines, phenylalanine, tryptophan, and oligo-peptides might be useful in conditioning the gut microenvironment, and thus, in the prevention and treatment of disorders such as inflammatory bowel disease (IBD), infectious enterocolitis, and other inflammatory and secretory diarrheal diseases. Here, we review the emerging roles of the CaSR in intestinal homeostasis and its therapeutic potential for gut pathology.
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Owen
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
authors.forename: Sam X
authors.initials: SX
authors.lastname: Cheng
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA; Division of Hepatology, Gastroenterology, and Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA; Division of Hepatology, Gastroenterology, and Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Bikash
authors.initials: B
authors.lastname: Sahay
authors.affiliation: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA; Division of Hepatology, Gastroenterology, and Nutrition, University of Florida, Gainesville, FL, USA. Electronic address: m.zadeh@ufl.edu.
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism; D003967:Diarrhea / Q000276:immunology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D044169:Receptors, Calcium-Sensing
keywords: Calcium-sensing receptor; Diarrhea; Intestinal inflammation; Intestinal permeability; Microbiota; Polyamines