Amino acid uptake by the cultured human placental trophoblast: Exogenous regulation

Summary 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 had demonstrated that α-(methylamino)isobutyric acid (MeAIB)-sensitive, α-aminoisobutyric acid (AIB) uptake by the cultured human placental trophoblast cells is stimulated by insulin. This study evaluated insulin like growth factor-1 (IGF-1) stimulation of AIB uptake in cultured human placental trophoblast cells. Na + -dependent AIB uptake was significantly stimulated by IGF-I in a time dependent manner, as early as 30 minutes. The maximum effect was at 2–4 hours of continuous exposure to IGF-I. Stimulation was dependent upon IGF-1 concentration. AIB uptake was inhibited by increasing concentrations of MeAIB. Approximately 75% of basal (unstimulated) AIB uptake was inhibited by MeAIB. The IGF-1 stimulated increment above basal AIB uptake was completely inhibited by MeAIB. At 200 ng/ml, stimulation was greater than IGF-1 than with IGF-1. The IGF-1 effect was inhibited by anti-IGF-1 receptor antibody, confirming mediation via IGF-1 receptor. In addition to the IGFs, treating the cultured trophoblast cells with 8-br-cAMP or PMA temporally stimulated AIB uptake. Therefore, Na + -dependent AIB uptake appears to be stimulated by factors which function via receptor tyrosine kinase and/or serine/threonine protein kinases (protein kinases A and C).