title: Structural specificity of mechanisms controlling the hepatic uptake and biliary output of methotrexate in the rat.
abstract: Using an in vivo model with systemic administration of compounds, the hepatic uptake from blood and hepatic release into bile of [3H]methotrexate [( 3H]MTX) are shown to involve structurally distinct and specific mechanisms. The hepatic uptake of [3H]MTX from blood is shown to proceed through two separate mechanisms: one inhibitable by the bile salt cholic acid, and the other inhibitable by either unlabeled MTX or folic acid, but not the lipophilic antifol, trimetrexate. The biliary output of [3H]MTX was shown to be related to the cholic acid-sensitive mechanism of hepatic uptake of [3H]MTX. In contrast, the biliary output of [3H]MTX was shown to be markedly stimulated by either unlabeled MTX or trimetrexate but not folic acid, demonstrating structural specificity for the biliary output of [3H]MTX distinct from the structural specificity shown for the hepatic uptake of [3H]MTX.
authors.forename: J C
authors.initials: JC
authors.lastname: Deutsch
authors.forename: J F
authors.initials: JF
authors.lastname: Kolhouse
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
chemical_list: D014316:Tritium; D008727:Methotrexate