SIGNALING ELEMENTS INVOLVED IN AMINO-ACID-TRANSPORT RESPONSES TO ALTERED MUSCLE-CELL VOLUME

Skeletal muscle glutamine uptake via the transport system N-m is subje ct to rapid (t(1/2) = approximate to 1 min) regulation after changes i n cell volume by mechanisms that remain to be elucidated. Wortmannin ( phosphatidylinositol 3-kinase inhibitor) but not rapamycin (inhibitor of p(70S6) kinase activation) prevents both hypo-osmotic swelling-indu ced stimulation and hyperosmotic shrinkage-induced inhibition of Na+-d ependent glutamine uptake in primary culture of rat skeletal muscle, G -protein inhibitors (cholera, pertussis toxins) also abolished respons es of glutamine transport to cell. volume changes whereas these respon ses were sustained in the presence of G-protein activators (MAS 7, lys ophosphatidic acid), Swelling-induced activation of glutamine transpor t does not seem to involve release of autocrine factors because ''cond itioned'' medium from swollen cells has no effect on previously unstim ulated cells, System A amino acid transport exhibits responses to cell volume change that are opposite to those of system N-m, but these are also blocked by wortmannin. Active phosphatidylinositol 3-kinase appe ars to be required to enable muscle cells to exhibit rapid, volume-ind uced changes in amino acid transport when suitably stimulated.