title: 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.
mesh_terms: D000409:Alanine / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002463:Cell Membrane Permeability; D005454:Fluorescence Polarization; D005947:Glucose / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
chemical_list: D008081:Liposomes; D008937:Mitomycins; D009004:Monosaccharide Transport Proteins; D016685:Mitomycin; D012964:Sodium; D005947:Glucose; D000409:Alanine