A study of small intestinal dipeptidases of rats: effect of vinblastine treatment

Activities of L-glycyl-L-valine and L-glycyl-L-leucine dipeptidase were studied in the mucosa of the small intestine of rats following intraperitoneal administration of vinblastine sulfate (1.0 mg/kg). Activities of these dipeptidases were depressed significantly; the effect was maximal between 4 and 5 h after the injection and lasted for more than 16 h. The depression in the enzyme activities reached even up to 95% when the alkaloid was administered repeatedly in 4-hourly intervals. The present results, showing a dose-dependent inhibitory effect on these dipeptidases, suggest a toxic effect on the enzymes in addition to simple inhibition resulting from a blockade of cell division. The former possibility was examined by incubating mucosal homogenates with various concentrations of the alkaloid for 30 min. Subsequent measurement of the activities showed a significant depression when the alkaloid concentration was raised to 10 microgram/mg wet mucosa. It is concluded that vinblastine sulfate not only arrests the mitosis of the crypts but influences, additionally, the enzymatic complements of the enterocytes.