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.
D000818:Animals; D004150:Dipeptidases / Q000378:metabolism*; D005260:Female; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology; D007583:Jejunum / Q000166:cytology / Q000201:enzymology*; D008938:Mitosis / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000494:pharmacology*
D014747:Vinblastine; D004150:Dipeptidases