Journal article

Publication year: 2005

Pages: 67-71

Journal: European Journal of Pharmacology

Volume number: 512

Issue number: 1

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2005.02.025

Publisher: Elsevier

Abstract: 

Ca2+-dependent secretagogues such as carbacbol induce a transient Cl- secretion followed by long-lasting inhibition (run-down) of secretion. In the colonic tumour cell line, T84, epidermal growth factor (EGF) inhibits Ca2+-dependent secretion, whereas antagonists of the EGF-signalling pathway slow down its run-down. The aim of the present study was to investigate whether a similar mechanism underlies the down-regulation of carbachol-induced Cl- secretion measured as change in short-circuit current (I-sc) in a native intestinal epithelium, i.e. rat distal colon.

In contrast to the colonic tumour cell line, EGF (1-100 mu g/l) induced a transient secretory I-sc 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 I-sc. 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 I-sc, 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 I-sc 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.

Harvard Citation style: Schultheiss, G. and Diener, M. (2005) The epidermal growth factor-pathway is not involved in down-regulation of Ca2+-induced Cl− secretion in rat distal colon, European Journal of Pharmacology, 512(1), pp. 67-71. https://doi.org/10.1016/j.ejphar.2005.02.025

APA Citation style: Schultheiss, G., & Diener, M. (2005). The epidermal growth factor-pathway is not involved in down-regulation of Ca2+-induced Cl− secretion in rat distal colon. European Journal of Pharmacology. 512(1), 67-71. https://doi.org/10.1016/j.ejphar.2005.02.025