Leukotriene D4-induced calcium signaling in human intestinal epithelial cells.

LTD4 induces a calcium signal that consists of a mobilization from internal stores regulated by PTX-insensitive G protein, Rho, and, an influx across the plasma membrane regulated by PTX-sensitive Gi protein in human intestinal epithelial cells. The LTD4 induced mobilization of Ca2+ is mediated by a PH domain dependent association between PLC-gamma 1 and G beta gamma subunits. This interaction requires Src kinase activity as well as the association of this kinase with PLC-gamma 1, suggesting a G beta gamma mediated recruitment of proteins to the plasma membrane and formation of a signaling complex which is essential for the downstream Ca2+ signal. We found a cAMP-dependent protein kinase activity upstream of tyrosine kinase(s) and downstream of Gi protein, that is essential for LTD4-induced Ca2+ influx. This model of the LTD4-induced Ca2+ signaling pathways in intestinal epithelial cells is outlined schematically in Fig. 1.