Journal article

Publication year: 2000

Pages: 875-885

Journal: British Journal of Pharmacology

Volume number: 130

Issue number: 4

ISSN: 0007-1188

Open access status: Green

DOI Link: https://doi.org/10.1038/sj.bjp.0703363

Publisher: Wiley

Abstract: 

1 The antisecretory effects of flufenamate in the rat distal colon were investigated with the Ussing-chamber and the patch-clamp method as well as by measurements of the intracellular Ca2+ concentration using fura-2-loaded isolated crypts.

2 Flufenamate (5 . 10(-4) mol l(-1)) suppressed the short-circuit current (Isc) induced by carbachol (5 . 10(-5) mol l(-1)), forskolin (5 . 10(-6) mol l(-1)) and the Isc induced by the membrane-permeable analogue of cyclic AMP, CPT-cyclic AMP (10(-4) mol l(-1)).

3 Indomethacin (10(-6)-10(-4) mol l(-1)) did not mimic the effect of flufenamate, indicating that the antisecretory effect of flufenamate is not related to the inhibition of the cyclo-oxygenase.

4 When the basolateral membrane was depolarized by a high K+ concentration and a Cl- current was induced by a mucosally directed Cl- gradient, the forskolin-stimulated Cl- current was blocked by flufenamate, indicating an inhibition of the cyclic AMP-stimulated apical Cl- conductance.

5 When the apical membrane was permeabilized by the ionophore, nystatin, flufenamate decreased the basolateral K+ conductance and inhibited the Na+-K+-ATPase.

6 Patch-clamp experiments revealed a variable effect of flufenamate on membrane currents. In seven out of 11 crypt cells the drug induced an increase of the K+ current, whereas in the remaining four cells an inhibition was observed.

7 Experiments with fura-2-loaded isolated crypts indicated that flufenamate increased the basal as well as the carbachol-stimulated intracellular Ca2+ concentration.

8 These results demonstrate that flufenamate possesses multiple action sites in the rat colon: The apical Cl- conductance, basolateral K+ conductances and the Na+-K+-ATPase.

Harvard Citation style: Schultheiss, G., Frings, M., Hollingshaus, G. and Diener, M. (2000) Multiple action sites of flufenamate on ion transport across the rat distal colon, British Journal of Pharmacology, 130(4), pp. 875-885. https://doi.org/10.1038/sj.bjp.0703363

APA Citation style: Schultheiss, G., Frings, M., Hollingshaus, G., & Diener, M. (2000). Multiple action sites of flufenamate on ion transport across the rat distal colon. British Journal of Pharmacology. 130(4), 875-885. https://doi.org/10.1038/sj.bjp.0703363