Neutral amino acid transport in astrocytes: characterization of Na+-dependent and Na+-independent components of alpha-aminoisobutyric acid uptake.
Neutral amino acid transport is largely unexplored in astrocytes, although a role for these cells in blood-brain barrier function is suggested by their close apposition to cerebrovascular endothelium. This study examined the uptake into mouse astrocyte cultures of alpha-aminoisobutyric acid (AIB), a synthetic model substrate for Na+-dependent system A transport. Na+-dependent uptake of AIB was characteristic of system A in its pH sensitivity, kinetic properties, regulatory control, and pattern of analog inhibition. The rate of system A transport declined markedly with increasing age of the astrocyte cultures. There was an unexpectedly active Na+-independent component of AIB uptake that declined less markedly than system A transport as culture age increased. Although the saturability of the Na+-independent component and its pattern of analog inhibition were consistent with system L transport, the following properties deviated: (1) virtually complete inhibition of Na+-independent AIB uptake by characteristic L system substrates, suggesting unusually high affinity of the transporter; (2) apparent absence of trans-stimulation of AIB influx; (3) unusually concentrative uptake at steady state (the estimated distribution ratio for 0.2 mM AIB was 55); and (4) susceptibility to inhibition by N-ethylmaleimide. Direct study of the uptake of system L substrates in astrocytes is needed to confirm the present indications of high affinity and concentrative Na+-independent transport.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010649:Phenylalanine / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology*; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; D007328:Insulin; C100049:2-aminoisobutyric acid; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D010649:Phenylalanine; D014364:Tryptophan; D012964:Sodium; D005033:Ethylmaleimide