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Regulation of amino acid uptake by phorbol esters and hypertonic solutions in rat thymocytes
Author(s) -
Klip Amira,
Mack Esther,
Cragoe Edward J.,
Grinstein Sergio
Publication year - 1986
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041270209
Subject(s) - cycloheximide , antiporter , amiloride , stimulation , amino acid , chemistry , proline , biochemistry , protein biosynthesis , medicine , endocrinology , sodium , biology , membrane , organic chemistry
Growth factors, mitogens, and malignant transformation can alter the rate of amino acid uptake in mammalian cells. It has been suggested that the effects of these stimuli on proliferation are mediated by activation of Na + /H + exchange. In lymphocytes, Na + /H + exchange can also be activated by phorbol esters and by hypertonic media. To determine the relationship between the cation antiport and amino acid transport, we tested the effects of these agents on the uptake of α‐aminoisobutyric acid (AIB), methyl‐AlB, proline, and leucine in rat thymocytes. Both 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and hypertonicity stimulated amino acid uptake through system A (AIB, proline, and methyl‐AlB). In addition, TPA, but not hypertonicity, also elevated leucine uptake. The stimulation of the Na + ‐dependent system A was not due to an increased inward electrochemical Na + gradient. The effects of TPA and hypertonic treatment were not identical: Stimulation of AIB uptake by TPA was observed within minutes, whereas at least 1 hr was required for the effect of hypertonicity to become noticeable. Moreover, stimulation by hypertonicity but not that by TPA, was partially inhibited by cycloheximide, suggesting a role of protein synthesis. That stimulation of Na + /H + exchange does not mediate the effects on amino acid transport is suggested by two findings: (1) the stimulation of AIB uptake was not prevented by concentrations of amiloride or of 5‐(N,N‐disubstituted) amiloride analogs that completely inhibit the Na + /H + antiport and (2) conditions that mimic the effect of the antiport, namely, increasing [Na + ] i or raising pH i failed to stimulate amino acid uptake. Thus, in lymphocytes, activation of Na + /H + exchange and stimulation of amino acid transport are not casually related.