title: Insulin-like growth factor-1 stimulates amino acid uptake by the cultured human placental trophoblast.
abstract: Amino acid uptake by the human placenta is known to occur via several transport mechanisms. However, regulation by extracellular factors has received relatively little attention. A recent report by this laboratory characterized the uptake of alpha-aminoisobutyric acid (AIB) stimulated by insulin in the cultured human placental trophoblast. The current study evaluated the effect of insulin-like growth factor-1 (IGF-1) on AIB uptake in cultured human placental trophoblasts. Na(+)-dependent AIB uptake was significantly stimulated by IGF-I in a time-dependent manner, as early as 30 min after hormone exposure. The maximum effect was at 2-4 hr of continuous exposure to IGF-I and the stimulation was dependent upon IGF-1 concentration approaching maximal stimulation at 50 ng.ml-1. AIB uptake was inhibited by increasing concentrations of alpha-(methylamino)isobutyric acid (MeAIB). Approximately 75% of basal (unstimulated) Na(+)-dependent AIB uptake was inhibited by MeAIB. The IGF-1-stimulated increment above basal AIB uptake was completely inhibited by MeAIB. IGF-1 increased the maximum uptake velocity but not Km. Using equimolar concentrations, stimulation was greater with IGF-1 than with IGF-2. Stimulation by IGF-1, but not insulin, was inhibited by anti-IGF-1 receptor antibody, indicating mediation via the IGF-1 receptor. H7, a nonspecific inhibitor of serine-threonine kinase, inhibited IGF-1-dependent stimulation of AIB uptake. In addition, calphostin C (a specific inhibitor of protein kinase C), but not H89 (a specific inhibitor of protein kinase A), inhibited the IGF-1 action. This study further characterizes regulated amino acid uptake by the human placental trophoblasts and demonstrates that the Na(+)-dependent component of AIB uptake is stimulated by physiologic concentrations of IGF-1.
authors.affiliation: Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
authors.forename: P I
authors.initials: PI
authors.lastname: Karl
mesh_terms: D000621:Aminoisobutyric Acids / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012964:Sodium / Q000378:metabolism; D013002:Somatomedins; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D000621:Aminoisobutyric Acids; D047428:Protein Kinase Inhibitors; D013002:Somatomedins; C100049:2-aminoisobutyric acid; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012964:Sodium