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Medline ® Abstract for Reference 7

of 'Enterotoxicity of chemotherapeutic agents'

Epidermal growth factor inhibits Ca(2+)-dependent Cl- transport in T84 human colonic epithelial cells.
Uribe JM, Gelbmann CM, Traynor-Kaplan AE, Barrett KE
Am J Physiol. 1996 Sep;271(3 Pt 1):C914-22.
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.
Department of Medicine, University of California, San Diego, School of Medicine 92103, USA.