Effects of diclofenac sodium and disodium ethylenediaminetetraacetate on electrical parameters of the mucosal membrane and their relation to the permeability enhancing effects in the rat jejunum.

Abstract

The effects of diclofenac sodium and disodium ethylenediaminetetraacetate (EDTA) on electrical parameters of rat jejunal membrane were investigated, together with measurement of the mucosal-to-serosal flux of sulphanilic acid or L-phenylalanine. Both adjuvants increased the flux rate of sulphanilic acid to a similar extent when added to the mucosal solution at 10 mM, but there were apparent differences in their effects on the electrical parameters. The addition of EDTA induced the gradual reduction in the membrane resistance (Rm) by 6-8 ohm cm-2, while the effect of diclofenac on Rm was complicated and concentration-dependent. The short circuit current (Isc) was reduced rapidly to the level of 30-40 microA cm-2 by the addition of diclofenac, but was less affected by EDTA. The flux rate of L-phenylalanine was decreased extensively by diclofenac or the 10 mM concentration of EDTA, suggesting an inhibition of carrier-mediated transport systems in the membrane. Together with our preceding communication (Yamashita et al 1985, J. Pharm. Pharmacol. 37: 512-513), it became obvious that the sites of action of diclofenac and EDTA were different, the former directly interacting with the epithelial cell to alter the permeability and functions of the cell membrane, while the primary effect of EDTA could be at the intercellular junctions.