Structural specificity of mechanisms controlling the hepatic uptake and biliary output of methotrexate in the rat.
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.
Deutsch
J C
JC
Kolhouse
J F
JF
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
D014316:Tritium; D008727:Methotrexate