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Uptake of Methotrexate-³H by Rabbit Kidney Slices

Laboratory of Chemical Pharmacology and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

Methotrexate-³H (MTX-³H) was accumulated against a concentration gradient by renal cortical slices. This accumulation was energy dependent, inhibited by metabolic inhibitors, Diamox, and high concentrations of ouabain.

Several folic 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 folic acid analog.

The accumulation of MTX-³H may represent transport from blood to urine and may be clinically important in predicting drug toxicity.

Received 1/11/66. Accepted 11/ 1/66.

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