INHIBITION OF METHIONINE TRANSPORT BY METHOTREXATE IN MITOGEN-STIMULATED HUMAN-LYMPHOCYTES

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 67  (7-8) , 631-639
Abstract
Mitogen stimulation of human lymphocytes was used to study the expression of several amino acid transport systems in response to cell growth. Resting lymphocytes possess detectable neutral amino acid transport systems which can be activated by phytohemagglutinin (PHA). Na-independent transport of 2-aminobicyclo (2,2,1)heptane 2-carboxylic acid was similar in resting and stimulated lymphocytes. Na-dependent uptake of methyl aminoisobutyric acid and .alpha.-aminoisobutyric acid increased 3- to 8-fold with stimulation by PHA. Methionine uptake was primarily Na-independent in resting lymphocytes; methionine uptake increased 4- to 8-fold in stimulated cells; most of this increase was attributable to Na-dependent transport. Uptake of methotrexate (MTX) was minimal in resting lymphocytes but was maximal 72 h after stimulation with PHA; this increase in MTX uptake was accompanied by inhibition of Na-dependent methionine transport. Apparently, PHA activates Na-dependent transport of methionine, and this activation is blocked by the folate antagonist, MTX. [MTX is an antineoplastic drug.].