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Tryptophan transport in human fibroblast cells-a functional characterization.
Örebro University.
Örebro University.
Uppsala University Hospital.
Örebro University.
2011 (English)In: International Journal of Tryptophan Research, ISSN 1178-6469, Vol. 4, 19-27 p.Article in journal (Refereed) Published
Abstract [en]

There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.Tryptophan kinetic parameters (V(max) and K(m)) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of (3)H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high V(max) and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower V(max) and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na(+)) dependent, while uptake at high substrate concentration was mainly Na(+) independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.

Place, publisher, year, edition, pages
2011. Vol. 4, 19-27 p.
National Category
Neurosciences
Research subject
Chemistry, Biochemistry
Identifiers
URN: urn:nbn:se:lnu:diva-52189DOI: 10.4137/IJTR.S6913PubMedID: 22084600OAI: oai:DiVA.org:lnu-52189DiVA: diva2:922349
Available from: 2016-04-22 Created: 2016-04-22 Last updated: 2016-04-25Bibliographically approved

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Vumma, Ravi
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CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
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