Transport of bestatin in rat renal brush-border membrane vesicles.
Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine] is a dipeptide, comprising L-leucine and an unusual beta-amino acid. We studied its transport mechanism in rat renal brush-border membrane vesicles. Uptake of cephradine, an aminocephalosporin, by isolated brush-border membrane vesicles was trans-stimulated and cis-inhibited by bestatin, indicating that these drugs are transported via the same transport system(s). The uptake of bestatin was trans-stimulated by preloading the vesicles with glycylsarcosine, and was cis-inhibited by substrates for the H+/dipeptide cotransport system. Bestatin inhibited tetraethylammonium (an organic cation) uptake, and bestatin uptake was cis-inhibited by substrates for the H+/organic cation antiport system. In addition, bestatin uptake was stimulated by an outward H+ gradient (the driving force for the H+/organic cation antiport system). These findings suggest that bestatin, in spite of being a dipeptide, is transported via not only the H+/dipeptide cotransport system but also the H+/organic cation antiport system in rat renal brush-border membrane.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
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Hori
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Tomita
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Katsura
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Yasuhara
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Inui
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Takano
D000818:Animals; D001692:Biological Transport; D002515:Cephradine / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D006033:Glycylglycine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D004151:Dipeptides; D013757:Tetraethylammonium Compounds; D006033:Glycylglycine; C004194:glycylsarcosine; D019789:Tetraethylammonium; D002515:Cephradine; D007930:Leucine; C012211:ubenimex