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Am J Physiol Regul Integr Comp Physiol 279: R1580-R1589, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 5, R1580-R1589, November 2000

Induction of BGT-1 and amino acid System A transport activities in endothelial cells exposed to hyperosmolarity

Pier-Giorgio Petronini1, Roberta R. Alfieri1, M. Nadia Losio2, Alessandro E. Caccamo1, Andrea Cavazzoni1, Mara A. Bonelli1, Angelo F. Borghetti1, and Kenneth P. Wheeler3

1 Dipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare e Immunologia, Università degli Studi di Parma, 43100 Parma; 2 Centro Substrati Cellulari, Istituto Zooprofilattico Sperimentale, 25125 Brescia, Italy; and 3 School of Biological Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom

We studied the responses to hypertonicity of cultured endothelial cells from swine pulmonary arteries. In 0.5 osmol/kgH2O medium, initial cell shrinkage was followed by a regulatory volume increase (RVI), complete after 1 h, concomitant with an increase in cellular K+ content. Then the activity of amino acid transport System A increased, accompanied by an accumulation of ninhydrin-positive solutes (NPS), reaching a peak at ~6 h. The subsequent decline in System A activity was paralleled by an induction of the betaine-GABA transporter (BGT-1), detected as increases of BGT-1 mRNA and of transport activity, which peaked at ~24 h. Inhibitors of transcription or translation prevented induction of both transport activities. The increased expression of BGT-1, which involved activation of "tonicity-responsive enhancer," was inhibited by 5 mM extracellular betaine. Cellular K+ concentration gradually declined after the accumulation of NPS and during the induction of BGT-1. This very effective adaptation to hypertonicity suggests it has a physiological role.

membrane transport; osmolyte; regulatory volume increase; volume


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