Effect of colchicine and vinblastine on rat intestinal water transport and Na-K-ATPase activity

Abstract

The hypothesis that colchicine and vinblastine, which are commonly used for therapeutic purposes and known to cause diarrhoea, decrease intestinal water transport by inhibition of Na-K-ATPase activity was tested in rats. Net fluid transport by jejunal segments was measured four hours after intraperitoneal injection of either 0.15 M NaCl (0.5 ml/100 g), colchicine (0.5 mg/100 g b.w.), or vinblastine (1.0 mg/100 g b.w.). Colchicine and vinblastine decreased net fluid transport: 3.0 +/- 0.9 (SE) and 4.6 +/- 0.4 (SE) respectively, as compared to that transported by segments from rats injected with 0.15 M NaCl, 8.6 +/- 0.7 (SE) g fluid/hour/g. Methylprednisolone (3.0 mg/100 g b.w.) abolished the inhibitory effect of cholchicine and vinblastine on fluid transport. Colchicine and vinblastine were found to decrease significantly mucosal Na-K-ATPase activity, 18.2 +/- 4.9 (SE); 25.2 +/- 2.4 (SE) respectively, as compared to that measured in rats injected with saline 40.6 +/- 3.4 (SE) mumol/mg protein/hour. Pretreatment with methylprednisolone prevented the decrease in enzyme activity observed in rats injected with colchicine and vinblastine. The degree of inhibition in intestinal Na-K-ATPase activity was similar to that observed in fluid transport following colchicine and vinblastine. It is thus suggested that colchicine-induced inhibition of water transport is caused by inhibition of Na-K-ATPase activity, an effect which can be prevented by pretreatment with methyl-prednisolone.