EPIDERMAL GROWTH-FACTOR INHIBITS CA2-DEPENDENT TRANSPORT IN T84 HUMANCOLONIC EPITHELIAL-CELLS()

This study examined whether epidermal growth factor (EGF) inhibits Ca2 +-dependent Cl- secretion by T84 cells. Basolateral EGF inhibited Cl- secretion induced by carbachol or thapsigargin, without blocking the r ise in intracellular Ca2+. Studies have shown that carbachol renders T 84 cells refractory to subsequent stimulation by thapsigargin, an effe ct ascribed to D-myo-inositol 3,4,5,6-tetrakisphosphate [D-Ins(3,4,5,6 )P-4]. EGF also increased DL-Ins(3,4,5,6)P-4 to a maximum of 170% abov e control. However, despite the fact that EGF inhibited Cl- secretion at 1 min, DL-Ins(3,4,5,6)P-4 was not elevated at this time point. EGF plus carbachol had a greater inhibitory effect on Cl- secretion than e ither alone, indicating the likely involvement of an additional inhibi tory pathway activated by EGF. Staurosporine did not alter the ability of EGF to inhibit Cl- secretion or increase DL-Ins(3,4,5,6)P-4. In co ntrast, genistein inhibited the rise in DL-Ins(3,4,5,6)P-4 and partial ly reversed EGF's inhibitory effect on Cl- secretion. In conclusion, E GF and carbachol can both inhibit Cl- secretion via D-Ins(3,4,5,6)P-4, whereas EGF also generates an additional inhibitory signal.