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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/G120    most recent 00226.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Justinich, C. J. Articles by MacLeod, R. J. PubMed PubMed Citation Articles by Justinich, C. J. Articles by MacLeod, R. J.

MUCOSAL BIOLOGY

The extracellular calcium-sensing receptor (CaSR) on human esophagus and evidence of expression of the CaSR on the esophageal epithelial cell line (HET-1A)

Pediatric Gastroenterology, Departments of ¹Pediatrics, ²Medicine, and ³Physiology, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario

Submitted 19 May 2006 ; accepted in final form 16 October 2007

Gastrointestinal reflux disease and eosinophilic esophagitis are characterized by basal cell hyperplasia. The extracellular calcium-sensing receptor (CaSR), a G protein-coupled receptor, which may be activated by divalent agonists, is expressed throughout the gastrointestinal system. The CaSR may regulate proliferation or differentiation, depending on cell type and tissue. The current experiments demonstrate the expression of the CaSR on a human esophageal epithelial cell line (HET-1A) and the location and expression of the CaSR in the human esophagus. CaSR immunoreactivity was seen in the basal layer of normal human esophagus. CaSR expression was confirmed in HET-1A cells by RT-PCR, immunocytochemistry, and Western blot analysis. CaSR stimulation by extracellular calcium or agonists, such as spermine or Mg²⁺, caused ERK1 and 2 activation, intracellular calcium concentration ([Ca²⁺]_i) mobilization (as assessed by microspecfluorometry using Fluo-4), and secretion of the multifunctional cytokine IL-8 (CX-CL8). HET-1A cells transiently transfected with small interfering (si)RNA duplex against the CaSR manifested attenuated responses to Ca²⁺ stimulation of phospho- (p)ERK1 and 2, [Ca²⁺]_i mobilization, and IL-8 secretion, whereas responses to acetylcholine (ACh) remained sustained. An inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC) (U73122 [GenBank] ) blocked CaSR-stimulated [Ca²⁺]_i release. We conclude that the CaSR is present on basal cells of the human esophagus and is present in a functional manner on the esophageal epithelial cell line, HET-1A.

basal cells; siRNA