RT Journal Article
SR Electronic
T1 Transport mechanisms of bestatin in rabbit intestinal brush-border membranes: role of H+/dipeptide cotransport system.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 859
OP 862
VO 252
IS 2
A1 Y Tomita
A1 T Katsura
A1 T Okano
A1 K Inui
A1 R Hori
YR 1990
UL http://jpet.aspetjournals.org/content/252/2/859.abstract
AB Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a potent inhibitor of aminopeptidase B and leucine aminopeptidase, enhances the immune response to activate the defense mechanism of the living organism and suppresses the growth and metastasis of cancer. Bestatin has been effectively used by p.o. administration, but the mechanisms of intestinal absorption remain to be solved. The present study was undertaken to examine whether bestatin, a dipeptide containing an unusual amino acid, is transported via dipeptide carriers in intestinal brush-border membranes, by using cephradine as a probe for the H+/dipeptide cotransport system. The initial uptake of cephradine in the presence or absence of an inward H+ gradient, driving force, was inhibited by bestatin and this inhibition occurred in a competitive manner (Ki = 0.47 mM). The uptake of cephradine was stimulated by the countertransport effect of bestatin, the definitive criterion for ascertaining a common transport system. These findings indicate that bestatin, as well as cephradine and other p.o. cephalosporins, can be transported via dipeptide carriers in intestinal brush-border membranes.