title: Signaling elements involved in amino acid transport responses to altered muscle cell volume.
abstract: 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.
authors.affiliation: Department of Anatomy and Physiology, University of Dundee, Scotland, U.K.
authors.forename: S Y
authors.initials: SY
authors.lastname: Low
authors.forename: M J
authors.initials: MJ
authors.lastname: Rennie
authors.forename: P M
authors.initials: PM
authors.lastname: Taylor
mesh_terms: D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D017077:Culture Media, Conditioned; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D005973:Glutamine / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008246:Lysophospholipids / Q000494:pharmacology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus; D012965:Sodium Chloride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D000730:Androstadienes; D002352:Carrier Proteins; D002772:Cholera Toxin; D017077:Culture Media, Conditioned; D003513:Cycloheximide; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D005973:Glutamine; D036341:Intercellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D011090:Polyenes; D047428:Protein Kinase Inhibitors; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D012965:Sodium Chloride; D010566:Virulence Factors, Bordetella; D000077191:Wortmannin; C084070:Mas7 protein, synthetic; C077738:sodium-dependent glutamine transporter