Albumin binding and brain uptake of 6-fluoro-DL-tryptophan: competition with L-tryptophan.
We investigated potential competition between L-tryptophan (TRP) and 6-fluoro-DL-tryptophan (6-F-TRP) for binding to albumin and for passage through the blood-brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 microM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants (Ka) of 3.7 +/- 0.04 x 10(4) and 0.62 +/- 0.01 x 10(4) M-1, respectively. Competitive inhibition was assessed as the decrease in the apparent Ka (K' a) of TRP in the presence of 6-F-TRP, with no modification of the N value. Competition between TRP, 6-F-TRP and L-valine (VAL) for passage across the BBB was demonstrated using two approaches. When administered concomitantly with TRP or 6-F-TRP to rats, VAL decreased brain uptake of TRP and 6-F-TRP and reversed their action on serotonin. In Oldendorf's model, 6-F-TRP and VAL decreased the brain uptake of TRP.
Chanut
E
E
Laboratoire de Pharmacologie, Faculté de Pharmacie, Châtenay-Malabry, France.
Zini
R
R
Trouvin
J H
JH
Riant
P
P
Tillement
J P
JP
Jacquot
C
C
D000818:Animals; D001667:Binding, Competitive; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism*; D014633:Valine / Q000378:metabolism
D012709:Serum Albumin; D012710:Serum Albumin, Bovine; C001244:6-fluorotryptophan; D014364:Tryptophan; D014633:Valine