Biopharmaceutical Study of the Hepato-biliary Transport of Drugs. II. Roles of the Liver Cytoplasmic Y and Z Binding Proteins and T Binder on the Hepato-biliary Transport of Organic Anionic Compounds
The roles of the rat liver cytoplasmic Y and Z binding proteins and T binder on the hepato-biliary transport of some organic anionic compounds, four non-metabolizing sulfonic acid dyes, bromphenol blue (BPB), bromthymol blue (BTB), amaranth (AM) and tartrazine (TZ) and a non-metabolizing carboxylic acid, p-acetylaminohippuric acid (PAAH) which are excreted into bile by an active transport system were investigated. No free form of these compounds was detected in the rat liver cytoplasmic fraction by means of the gel filtration of the liver 100000 g (av.) supernatant using a column of Sephadex G-75 following the intravenous administration of these compounds, and these compounds were in common bound to Y binding protein. In addition BPB and BTB of which the liver/plasma concentration ratios were greater than one were bound to Z binding protein but AM, TZ and PAAH of which the liver/plasma concentration ratios were equal or less than one were not bound to Z binding protein. When sulfobromophthalein, 5 times molar ratio to BPB, was pre-administered to rats, the binding of BPB to Y binding protein was decreased 65% but the binding to Z binding protein was reversely increased 27%. Kinetical experiment showed that the binding of BPB to Y binding protein followed a hyperbolic curve and reached maximum at 15 min after the administration whereas the binding to Z binding protein was more slowly increased.