Secretory effect of azodisalicylate (azodisal sodium) on the short circuited mucosa of the rat ileum in vitro.
Azodisalicylate (ADS) is one of the newly developed substitutes of sulphasalazine consisting of two molecules of 5-amino-salicylic acid. Azodisalicylate caused diarrhoea in some patients, apparently caused by an antiabsorptive secretagogue action of this compound. The mechanism of this was studied in the short circuited isolated mucosa of the rat ileum. Mucosal addition of ADS increased the potential difference (PD) and short circuit current (Isc) at a concentration of 1.3.10(-4) mol/l (4 mg/dl) with maximal effects at 1.3.10(-3) mol/l (40 mg/dl). Epithelial resistance was only slightly decreased at the higher concentrations of 40 and 100 mg/dl. Serosal ADS had no effect on electrical parameters. The increase of Isc was associated with a change of net chloride absorption into net secretion. Net sodium absorption was only slightly and not significantly decreased. The changes were reversible after rinsing away the ADS. Treatment of the mucosa with furosemide inhibited the ADS induced increase of Isc, suggesting transcellular pathway for the ADS stimulated secretion. Biosynthesis of prostaglandins is not involved in the mechanism of this secretion, as treatment with indomethacin did not alter the effect of ADS on Isc. Results suggest that ADS can be considered as a secretagogue, which stimulates intestinal secretion via a transcellular pathway. Because of the bacterial cleavage of the double molecule into two molecules of the non-secretagogue 5-amino-salicylic acid in the colon, however, diarrhoea may develop only in patients with a decreased absorptive capacity of the colon, or insufficient cleavage of ADS.
Goerg
K J
KJ
First Medical Clinic of the Johannes Gutenberg University, Mainz, FRG.
Wanitschke
R
R
Diehl
P H
PH
Meyer zum Büschenfelde
K H
KH
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects; D005665:Furosemide / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D000636:Aminosalicylic Acids; D002712:Chlorides; D005665:Furosemide; D012964:Sodium; C032587:olsalazine; D007213:Indomethacin