Journal article

Publication year: 1995

Pages: 309-314

Journal: Naunyn-Schmiedeberg's Archives of Pharmacology

Volume number: 351

Issue number: 3

ISSN: 0028-1298

DOI Link: https://doi.org/10.1007/BF00233252

Publisher: Springer

Abstract: 
human cancer. One of the side-effects of irinotecan is a strong diarrhoea. In order to investigate the mechanism underlying this diarrhoea, the effect of irinotecan on anion secretion across the isolated rat distal colon was studied. Irinotecan caused a concentration-dependent increase in short-circuit current (Isc). The increase in Isc was completely dependent on the presence of Cl- ions and was supressed by furosemide and the Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), indicating that it is caused by a Cl- secretion. The secretory response was inhibited by indomethacin, 1-benzylimidazole, a thromboxane synthase inhibitor, and SKandF 88046 ((N,N'-bis [7-(3-Chlorobenzeneaminosulfonyl)-1,2,3, rahydroisoquinolyl)disulfonylimide), a thromboxane A, receptor blocker. In isolated crypts irinotecan had no effect on the membrane potential. Consequently, the secretion induced by irinotecan is an indirect one, caused by the stimulation of eicosanoid production, e.g. thromboxane A(2), in the subepithelial tissue.

Harvard Citation style: Sakai, H., Diener, M., Gartmann, V. and Takeguchi, N. (1995) Eicosanoid-mediated Cl− secretion induced by the antitumor drug, irinotecan (CPT-11), in the rat colon, Naunyn-Schmiedeberg's Archives of Pharmacology, 351(3), pp. 309-314. https://doi.org/10.1007/BF00233252

APA Citation style: Sakai, H., Diener, M., Gartmann, V., & Takeguchi, N. (1995). Eicosanoid-mediated Cl− secretion induced by the antitumor drug, irinotecan (CPT-11), in the rat colon. Naunyn-Schmiedeberg's Archives of Pharmacology. 351(3), 309-314. https://doi.org/10.1007/BF00233252