Epidermal growth factor inhibits Ca(2+)-dependent Cl- transport in T84 human colonic epithelial cells.
This study examined whether epidermal growth factor (EGF) inhibits Ca(2+)-dependent Cl- secretion by T84 cells. Basolateral EGF inhibited Cl- secretion induced by carbachol or thapsigargin, without blocking the rise in intracellular Ca2+. Studies have shown that carbachol renders T84 cells refractory to subsequent stimulation by thapsigargin, an effect ascribed to D-myo-inositol 3,4,5,6-tetrakisphosphate [D-Ins(3,4,5,6)P4]. EGF also increased DL-Ins(3,4,5,6)P4 to a maximum of 170% above control. However, despite the fact that EGF inhibited Cl- secretion at 1 min, DL-Ins(3,4,5,6)P4 was not elevated at this time point. EGF plus carbachol had a greater inhibitory effect on Cl- secretion than either alone, indicating the likely involvement of an additional inhibitory pathway activated by EGF. Staurosporine did not alter the ability of EGF to inhibit Cl- secretion or increase DL-Ins(3,4,5,6)P4. In contrast, genistein inhibited the rise in DL-Ins(3,4,5,6)P4 and partially reversed EGF's inhibitory effect on Cl- secretion. In conclusion, EGF and carbachol can both inhibit Cl- secretion via D-Ins(3,4,5,6)P4, whereas EGF also generates an additional inhibitory signal.
Uribe
J M
JM
Department of Medicine, University of California, San Diego, School of Medicine 92103, USA.
Gelbmann
C M
CM
Traynor-Kaplan
A E
AE
Barrett
K E
KE
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects
D002712:Chlorides; D004815:Epidermal Growth Factor; D002118:Calcium