RT Journal Article SR Electronic T1 Structural specificity of mechanisms controlling the hepatic uptake and biliary output of methotrexate in the rat. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 221 OP 226 VO 250 IS 1 A1 J C Deutsch A1 J F Kolhouse YR 1989 UL http://jpet.aspetjournals.org/content/250/1/221.abstract AB 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.