Cortisol-induced inhibition of amino acid transport in thymic lymphocytes: Kinetic parameters: relation to ATP levels and protein synthesis; and specificity

Daniel T. Baran, William A. Peck, Patrick A. Frengley, Marshall A. Lichtman

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    19 Scopus citations

    Abstract

    1. 1. α-Aminoisobutyric acid accumulation in rat thymic lymphocytes increased in linear fashion for 10 min and reached an apparent steady state in 60 min. α-Aminoisobutyric acid was transported by concentrative and non-concentrative processes. Cortisol inhibited only the concentrative process. Inhibition was non-competitive, indicating a decrase in the total capacity of the active transport mechanism. The effect of cortisol on α-aminoisobutyric acid transport was evident only after 60-90 min of treatment but preceeded the appearance of reductions in cellular ATP by an additional 60-90 min, suggesting that cortisol inhibition of α-aminoisobutyric acid transport was not caused by the decrease in ATP. 2. 2. Inhibition of protein synthesis with cycloheximide reduced α-aminoisobutyric acid uptake without decreasing cellular ATP, pointing to the participation of labile proteins in the active transport of α-aminoisobutyric acid which are not related to ATP metabolism. Inhibition of α-aminoisobutyric acid transport caused by cortisol and cycloheximide together was no greater than that caused by each agent alone. Moreover, cortisol failed to decrease cellular ATP levels during simultaneous exopsure of thymic lymphocytes to cycloheximide. Hence, inhibition of α-aminoisobutyric acid transport and reduction of ATP content are separate manifestations of cortisol action, each arising by a process which depends upon de novo protein synthesis. 3. 3. Inhibition of α-aminoisobutyric acid transport by cortisol appeared to be related to its glucocorticoid activity sicne (a) low concentrations (0.1 μM and 1.0 μM) were inhibitory, yet steroids devoid of glucocorticoid activity (progresterone, cortisone and testosterone) were non-inhibitory at the same concentrations, and (b) 11-deoxy-cortisol (cortexolone), which is known to impede the binding of glucocorticoids to cellular receptors, appreciably reduced the degree of inhibition caused by cortisol. High concentrations of progesterone and cortisone (10 μM) inhibited α-aminoisobutyric acid transport slightly suggesting that the decrease in α-aminoisobutyric acid uptake caused by 10 μM cortisol might reflect both specific (glucocorticoid-related) and non-specific effects.

    Original languageEnglish
    Pages (from-to)627-639
    Number of pages13
    JournalBBA - Biomembranes
    Volume307
    Issue number3
    DOIs
    StatePublished - May 25 1973

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