title: Effect of various chemical modifiers on H+ coupled transport of cephradine via dipeptide carriers in rabbit intestinal brush-border membranes: role of histidine residues.
abstract: We examined the effect of diethylpyrocarbonate (DEPC), a histidine specific reagent, on H+ coupled transport of cephradine via dipeptide carriers in the intestinal brush-border membranes, in comparison with the effects of other chemical modifiers. Pretreatment of membrane vesicles with DEPC resulted in the inhibition of cephradine transport in the presence or absence of an inward H+ gradient. This inhibition was reversed by subsequent treatment with hydroxylamine, but not with dithiothreitol. The inactivation by DEPC pretreatment was abolished by the presence of cephradine or glycylsarcosine. In the DEPC-pretreated membranes, the V(max) value of cephradine uptake was decreased without any change in the Km value. In contrast, cephradine uptake was not changed by the pretreatment with N-acetylimidazole, a tyrosine specific reagent, or p-chloromercuribenzene sulfonate, a sulfhydryl reagent. These results suggest that histidine residues in the carriers are essential for H+ coupled transport of amiocephalosporins.
authors: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors: M
authors: M
authors: Kato
authors: H
authors: H
authors: Maegawa
authors: T
authors: T
authors: Okano
authors: K
authors: K
authors: Inui
authors: R
authors: R
authors: Hori
mesh_terms: D000818:Animals; D001692:Biological Transport; D002511:Cephalosporins / Q000493:pharmacokinetics*; D002515:Cephradine / Q000493:pharmacokinetics*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006639:Histidine / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits
chemical_list: D002511:Cephalosporins; D004151:Dipeptides; D006898:Hydroxylamines; D019811:Hydroxylamine; D006639:Histidine; D002515:Cephradine; D004047:Diethyl Pyrocarbonate; D004229:Dithiothreitol