Role of Calcium‐Sensing Receptor in Esophageal Epithelium

Abstract

The calcium sensing receptor (CaSR), a G‐protein coupled receptor, senses changes in extracellular Ca+2 and mediates its effects on cellular functions. In cells not directly involved in Ca+2 homeostasis, CaSR plays a role in many cellular processes including differentiation, proliferation and secretion. We investigated the role of CaSR in modulating esophageal barrier function. We used immunohistochemistry, Western blotting and PCR to identify CaSR and cell‐cell adhesion molecules in pig esophageal stratified squamous epithelium (SSE). In primary cultures of SSE, we investigated the effect of CaSR agonist (cinacalcet, CCT) and antagonist, calhex, on cell growth and cell‐cell junction formation. We used MTT assay to monitor proliferation under different conditions that affect CaSR activity. SSE cells exposed to CCT (2.5μM, 24 hours), changed from polygonal to spindle‐shaped cells, a transformation proportional to CCT concentration. Staining with E‐cadherin and β‐catenin antibodies, showed altered distribution of these proteins in CCT treated cells. Our results indicate: 1) CaSR is expressed in supra‐basal cells of esophageal epithelium but not in differentiated apical layers; 2) CaSR activation decreases the rate of growth of SSE in culture; 3) CaSR activity alters expression and distribution of intercellular adhesion proteins and could modulate barrier properties of esophageal epithelium. Support: VA Merit grant and Tulane Enhancement Funds