title: Inhibitory effects of amino-acid fluids on drug binding to site II of human serum albumin in vitro.
abstract: The effects of amino-acid fluids on ligand binding to human serum albumin (HSA) were investigated by fluorescence and ultrafiltration techniques. Warfarin and dansylsarcosine were used as the site marker fluorescence probes for site I and site II of HSA, respectively. Amino-acid fluids specifically decreased the fluorescence intensity induced by dansylsarcosine-HSA binding without any effects on that induced by warfarin-HSA binding. The ultrafiltration technique clarified that the free fraction of the site II drug, diazepam, in human serum was increased in the presence of amino-acid fluids, while no effect was observed in the free fraction of the site I drug, warfarin. The potencies of the effect on binding to site II, observed by fluorescence and ultrafiltration techniques, correlated well with the L-tryptophan contents in amino-acid fluids or with those in L-tryptophan solutions. Based on the comparison between the effects of amino-acid fluids and L-tryptophan solutions, we confirmed that L-tryptophan in amino-acid fluids specifically inhibits drug binding to site II of HSA.
authors.affiliation: Department of Pharmacy, Miyazaki Medical College Hospital, Kihara, Miyazaki-gun, Japan. kcyama@fc.miyazaki-u.ac.jp
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kuga
authors.forename: Norito
authors.initials: N
authors.lastname: Takamura
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Furuya
authors.forename: Muneaki
authors.initials: M
authors.lastname: Hidaka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Iwakiri
authors.forename: Ryuuichi
authors.initials: R
authors.lastname: Nishii
authors.forename: Manabu
authors.initials: M
authors.lastname: Okumura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kodama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arimori
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D006801:Humans; D008297:Male; D010288:Parenteral Nutrition; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012709:Serum Albumin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D004364:Pharmaceutical Preparations; D011955:Receptors, Drug; D012709:Serum Albumin