The FASEB Journal, Vol 11, 1111-1117, Copyright © 1997 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Signaling elements involved in amino acid transport responses to altered muscle cell volume

SY Low, MJ Rennie and PM Taylor
Department of Anatomy and Physiology, University of Dundee, Scotland, U.K.

Skeletal muscle glutamine uptake via the transport system Nm is subject to rapid (t(1/2) = approximately 1 min) regulation after changes in cell volume by mechanisms that remain to be elucidated. Wortmannin (phosphatidylinositol 3-kinase inhibitor) but not rapamycin (inhibitor of p70S6 kinase activation) prevents both hypo-osmotic swelling-induced stimulation and hyperosmotic shrinkage-induced inhibition of Na+- dependent glutamine uptake in primary culture of rat skeletal muscle. G- protein inhibitors (cholera, pertussis toxins) also abolished responses of glutamine transport to cell volume changes whereas these responses were sustained in the presence of G-protein activators (MAS 7, lysophosphatidic acid). Swelling-induced activation of glutamine transport does not seem to involve release of autocrine factors because "conditioned" medium from swollen cells has no effect on previously unstimulated cells. System A amino acid transport exhibits responses to cell volume change that are opposite to those of system Nm, but these are also blocked by wortmannin. Active phosphatidylinositol 3-kinase appears to be required to enable muscle cells to exhibit rapid, volume- induced changes in amino acid transport when suitably stimulated.

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