TRANSPORT OF METHOTREXATE IN CORTICAL SLICES OF MONKEY KIDNEY - EFFECT OF ORGANIC-ANIONS AND VINCRISTINE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (3) , 645-649
Abstract
Thin cortical slices of cynamolgus and rhesus monkey kidney were used to study the renal transport of [the antineoplastic drug] methotrexate (MTX). In experiments with renal cortical slices, MTX uptake at 25.degree. C was linear over the initial 30 min and was temperature-dependent. The Km was 0.094 mM for MTX uptake at 25.degree. C; Vmax was 0.098 .mu.mol/g of tissue per 30 min. In the presence of 1 mM, 2,4-dinitrophenol, p-aminohippurate or acetylsalicylate, MTX uptake was competitively inhibited. 2,4-Dinitrophenol had the greatest and acetylsalicylate had the least inhibitory effect. Folinic acid, folic acid and ouabain produced little or no effect on MTX uptake. MTX efflux from preloaded slices (preincubated with 0.5 mM MTX for 45 min) was a 1st-order process with T1/2 [half-life] of 7.13 .+-. 0.86 min. In the presence of vincristine or p-aminohippurate the T1/2 for MTX were 15.25 .+-. 0.91 and 4.59 .+-. 0.47 min, respectively. Thus, vincristine, an organic base, augmented MTX uptake, due to a reduction in the rate of efflux of MTX from the cortical tissues; p-aminohippurate, an organic acid, decreased MTX intracellular concentration by blocking influx and stimulating efflux. The renal transport of MTX in monkey kidney is apparently mediated predominantly by an organic anion secretory process; there is probably little or no reabsorptive transport.