Transport of L-phenylalanine and related amino acids at the ovine blood-brain barrier.
1. Unidirectional influx of amino acids at the blood-brain barrier was studied in the lamb and sheep under barbiturate anaesthesia using the single-pass indicator-dilution technique. 2. In the lamb, influx of both L-phenylalanine (14 +/- 1 nmol g-1 min-1) and L-alanine (12 +/- 2 nmol g-1 min-1) was greater than in the sheep: L-phenylalanine influx, 9 +/- 1 nmol g-1 min-1; L-alanine influx, 5 +/- 1 nmol g-1 min-1 (P less than 0.01). This difference reflected higher blood concentrations of these amino acids in the younger animal. 3. The kinetic parameters of transport for L-phenylalanine were determined in the lamb and sheep from measurements of influx over a range of blood concentrations. The concentration dependence of L-phenylalanine influx was best described by a model with a saturable and non-saturable component. Maximum influx (Jmax) was higher and apparent transport constant (km, app) lower in the lamb. Values obtained (mean +/- S.E.M.) were: lamb, Jmax, 138 +/- 6 nmol g-1 min; km, app, 0.85 +/- 0.10 mmol l-1; sheep, Jmax, 107 +/- 7 nmol g-1 min-1; km, app, 2.25 +/- 0.25 mmol l-1. 4. L-Phenylalanine inhibited influx of L-leucine, L-tyrosine, L-valine and L-glutamine but not L-arginine and L-lysine. Its influx was inhibited by L-histidine, L-valine and L-leucine, but not by L-glutamine or L-alanine. In the lamb, L-phenylalanine inhibited L-histidine influx with an apparent inhibitor constant (kh) of 139 mumol l-1, and a maximum inhibition of 92%. In the sheep, L-phenylalanine inhibited L-methionine influx with an apparent kh of 33 mumol l-1 and a maximum inhibition of 82%. 5. Fractional extraction of phenylalanine and alanine was stereospecific with preference for the L-enantiomer. In the lamb, fractional extraction values (mean +/- S.E.M.) were: L-phenylalanine, 0.58 +/- 0.03; D-phenylalanine, 0.20 +/- 0.02; L-alanine, 0.16 +/- 0.03; D-alanine, 0.05 +/- 0.02. Self-inhibition of extraction was evident for L-phenylalanine and L-alanine in both lamb and sheep.
Brenton
D P
DP
Department of Paediatrics, University College London, Rayne Institute.
Gardiner
R M
RM
D000596:Amino Acids / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D010649:Phenylalanine / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep / Q000378:metabolism*; D013237:Stereoisomerism
D000596:Amino Acids; D010649:Phenylalanine