Tyrosine transport in fibroblasts from healthy volunteers and patients with schizophrenia.
Aberrant tyrosine transport across the fibroblast membrane, as measured by lower Vmax and/or lower Km is a repeated finding in patients with schizophrenia. The aim of this study was to investigate the importance of two major transporters, the L- and A-systems and tyrosine transport in fibroblast cell lines from patients with schizophrenia and healthy volunteers. Fibroblast cell lines, n=6 from healthy volunteers and n=6 from patients with schizophrenia, were included in the study. Uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in absence and presence of inhibitors. The uptake of tyrosine by the L-system was evaluated with the inhibitor 2-aminobicyclo heptane-2-carboxylic acid (BCH) and the A-system with the inhibitor nonmetabolized methyl-aminoisobutyric acid (MeAIB). Using [14-C] MeAIB the functionality of system A isoform 2, ATA2, was tested. BCH inhibited the uptake of tyrosine with 90%, showing that tyrosine transport in fibroblasts is mainly transported by the L-system. Not more than 10% could be contributed by the A-system. Excess of MeAIB did not influence tyrosine kinetics. Moreover, MeAIB kinetics did not differ between the patients and the controls. In conclusion, aberrant tyrosine transport observed in patients with schizophrenia is probably linked to the one of the L-systems and does not seem to involve the ATA2 transporter.
Olsson
Emma
E
Department of Clinical Medicine, Division of Biomedicine, Orebro University, SE-701 82 Orebro, Sweden.
Wiesel
Frits-axel
FA
Bjerkenstedt
Lars
L
Venizelos
Nikolaos
N
D000328:Adult; D000598:Amino Acids, Cyclic / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology*; D002247:Carbon Isotopes / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D012559:Schizophrenia / Q000473:pathology*; D014443:Tyrosine / Q000378:metabolism* / Q000494:pharmacology; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D000598:Amino Acids, Cyclic; D002247:Carbon Isotopes; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D014443:Tyrosine