The epidermal growth factor-pathway is not involved in down-regulation of Ca2+-induced Cl− secretion in rat distal colon

In contrast to the colonic tumour cell line, EGF (1-100 μg/l) induced a transient secretory Isc and did not interfere with a subsequent administration of carbachol. Pretreatment with inhibitors of enzymes involved in the signalling cascade induced by EGF, i.e. tyrphostin AG1478, an inhibitor of the EGF receptor protein tyrosine kinase, PD 98059, an inhibitor of MAP kinase, and wortmannin, a blocker of the phosphatidylinositol-3-kinase, did also not affect the action of carbachol on transepithelial Isc. In order to investigate potential effects of these inhibitors on apical Cl− channels, the basolateral membrane was depolarized and a Cl− current across the apical membrane was driven by a Cl− gradient. Under these conditions, carbachol evoked a transient increase in Isc, caused by the stimulation of Ca2+-dependent Cl− channels, followed by a long-lasting down-regulation of apical Cl− conductance leading to a decrease in Isc. All blockers of the EGF-signalling pathway tested did not interfere with the action of carbachol at the apical membrane. Consequently, the EGF-pathway seems not to be involved in the down-regulation of Ca2+-dependent Cl− secretion across rat colon.