Uptake of methotrexate-3H by rabbit kidney slices.

Methotrexate-3H (MTX-3H) was accumulated against a con centration gradient by renal cortical slices. This accumulation was energy dependent, inhibited by metabolic inhibitors, Diamox, and high concentrations of ouabain. Several folie acid analogs containing the pteridine ring were inhibitors of this accumulation while certain weak organic acids were less striking inhibitors. This suggests that MTX-3H is carrier transported into cells nonspecifically as a weak organic acid and specifically as a folie acid analog. The accumulation of MTX-3H may represent transport from blood to urine and may be clinically important in predicting drug toxicity.