Decreased transport of d-glucose and l-alanine across brush-border membrane vesicles from small intestine of rats treated with mitomycin C

Abstract

To elucidate the mechanisms underlying the dysfunctions of intestinal absorption induced by antitumor drugs, the effect of pretreatment with mitomycin C on sodium gradient-dependent d-glucose and l-alanine transports was studied in rat brush-border membrane vesicles. 24, 48, 96, or 120 h following a single intravenous injection of mitomycin C, brush-border membrane vesicles were prepared from rat small-intestines. The uptake of d-glucose and l-alanine was shown to be Na + gradient-dependent even in the case of vesicles obtained from mitomycin C-treated rats, but uptake rates measured at 15 s and magnitude of overshooting effect in uptake of both solutes were decreased in vesicles maximally from 48 h mitomycin C-treated rats. The rate of d-glucose uptake calculated at 15 s recovered to the control level in vesicles prepared at 96 h and 120 h after mitomycin C-treatment, indicating that the effect of mitomycin C on Na + gradient-dependent d-glucose transport would be fully reversible. Tracer exchange experiments under Na + and d-glucose equilibrated conditions indicated that the Na +/ d-glucose transporters were similarly operative in the vesicles from control and 48 h mitomycin C-treated rats. Rates of 22Na + uptake measured at 15 s in vesicles from 48 h mitomycin C-treated rats, however, were increased. The increased permeability to Na + might bring about a more rapid dissipation of the Na + gradient in these vesicles and this would secondarily cause the decrease in Na +-dependent d-glucose uptake in vesicles from mitomycin C-treated rats.