Amino acid and putative neurotransmitter transport in human Y79 retinoblastoma cells. Effect of insulin and insulin-like growth factor.
The binding of insulin and insulin-like growth factor I (IGF-I) and their effect on amino acid and neurotransmitter transport was studied in cultured human Y79 retinoblastoma cells. Y79 cells possess specific receptors for both insulin and IGF-I. Insulin binding to Y79 cells is characterized by a curvilinear Scatchard plot suggesting a two-site or two-affinity binding system. In contrast, IGF-I binding has a linear plot indicative of a one-site, one-affinity binding system. The uptake of glycine, a putative neurotransmitter in the retina occurs by a specific transport system in Y79 cells, independent of the uptake of other neutral amino acids. The uptake of glycine was increased 25-50% by either insulin or IGF-I. The response to insulin or IGF-I on glycine uptake is gradual and concentration dependent. The accumulation of other amino acids and putative retinal neurotransmitters by Y79 cells was not significantly affected by insulin of IGF-I. In addition, the activity of Na+/K+-ATPase was not influenced. The analysis of high affinity glycine uptake indicates that insulin and IGF-I are stimulating glycine transport by increasing the V'max without significantly affecting the K'm. Further analysis suggests that insulin and IGF-I are causing a recruitment of additional glycine transporters at the cell surface or activating otherwise nonfunctional transporters by an unexplained mechanism. Because of the implication that glycine responds as a neuroactive amino acid in Y79 cells these studies suggest that insulin and IGF-I may influence neuroactivity in the human retina by regulating the transport of glycine.
D000596:Amino Acids / Q000378:metabolism*; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005134:Eye Neoplasms / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D017451:Receptors, Somatomedin; D012175:Retinoblastoma / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*
D000596:Amino Acids; D007328:Insulin; D018377:Neurotransmitter Agents; D017451:Receptors, Somatomedin; D013002:Somatomedins; C008147:insulin, iodo-; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D005998:Glycine