Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion

Abstract

The calcium-sensing receptor (CaSR) is activated by extracellular calcium (Ca[Formula: see text]) and mediates many of the known effects of extracellular divalent minerals on body cells. Both surface and crypt cells express CaSR transcripts and protein on both apical and basolateral surfaces. Raising Ca[Formula: see text] elicited increases in intracellular calcium (Ca[Formula: see text]) in both surface and crypt cells with an EC50 of 2 mM. The Ca[Formula: see text]-induced increase in Ca[Formula: see text] was associated with increases in inositol 1,4,5-trisphosphate and eliminated by U-73129, an inhibitor of phosphatidylinositol-phospholipase C, as well as by thapsigargin. Other CaSR agonists, Gd3+ and neomycin, mimicked these Ca[Formula: see text]-induced responses. Both luminal and bath Ca[Formula: see text], Gd3+, and neomycin induced increases in Ca[Formula: see text] in isolated perfused crypts. The stimulatory effect of forskolin on net fluid secretion in perfused crypts was abolished by increasing Ca[Formula: see text] in either luminal or bath perfusates. Thus both apical and basolateral CaSR on crypt cells are functional and provide pathways modulating net intestinal fluid transport that may have important implications for the prevention and treatment of certain diarrheal diseases associated with elevated cAMP.