RT Journal Article
SR Electronic
T1 H+ coupled active transport of bestatin via the dipeptide transport system in rabbit intestinal brush-border membranes.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 482
OP 486
VO 260
IS 2
A1 K Inui
A1 Y Tomita
A1 T Katsura
A1 T Okano
A1 M Takano
A1 R Hori
YR 1992
UL http://jpet.aspetjournals.org/content/260/2/482.abstract
AB 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.