H+ coupled active transport of bestatin via the dipeptide transport system in rabbit intestinal brush-border membranes.
Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a dipeptide containing an unusual amino acid, has been used clinically as an anticancer agent in p.o. dosage form. We examined the transport characteristics of [3H]bestatin by rabbit intestinal brush-border membrane vesicles. Bestatin uptake was stimulated by an inward H+ gradient (overshoot phenomenon) and by an interior-negative membrane potential. About half of the apparent bestatin uptake at 1 mM by brush-border membrane vesicles was estimated as binding to the membranes. The affinity constant for the bestatin transport was 0.52 mM. The uptake of bestatin by brush-border membrane vesicles was inhibited by p.o. cephalosporins and dipeptides, but not by amino acids. In vesicles preloaded with either bestatin, cephradine or glycylsarcosine, the uptake of [3H]bestatin was stimulated markedly (countertransport effect). These results indicate that bestatin is transported via the H+/dipeptide transport system in rabbit intestinal brush-border membranes.
Inui
K
K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
Tomita
Y
Y
Katsura
T
T
Okano
T
T
Takano
M
M
Hori
R
R
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001693:Biological Transport, Active; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002515:Cephradine / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism* / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism* / Q000502:physiology; D009994:Osmolar Concentration; D011817:Rabbits
D000903:Antibiotics, Antineoplastic; D004151:Dipeptides; C004194:glycylsarcosine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D006859:Hydrogen; D000626:Aminopeptidases; D002515:Cephradine; D007930:Leucine; C012211:ubenimex