Journal of Neural Transmission

, Volume 125, Issue 6, pp 899–912 | Cite as

Kynurenic acid and its derivatives are able to modulate the adhesion and locomotion of brain endothelial cells

  • Eszter Lajkó
  • Bernadett Tuka
  • Ferenc Fülöp
  • István Krizbai
  • József Toldi
  • Kálmán Magyar
  • László Vécsei
  • László KőhidaiEmail author
Translational Neurosciences - Original Article


The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood–brain barrier (BBB)] are well established. Cell–extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium. The effects of KYNA and its derivatives on cell adhesion were measured using an impedance-based technique, the xCELLigence SP system. Holographic microscopy (Holomonitor M4) was used to analyse both chemokinetic responses and morphometry. The GP8 cells proved to be a suitable model cell line for investigating cell adhesion and the locomotion modulator effects of kynurenines. KYNA enhanced cell adhesion and spreading, and also decreased the migration/motility of GP8 cells at physiological concentrations (10−9 and 10−7 mol/L). The derivatives containing an amide side-chain at the C2 position (KYNA-A1 and A2) had lower adhesion inducer effects compared to KYNA. All synthetic analogues (except KYNA-A5) had a time-dependent inhibitory effect on GP8 cell adhesion at a supraphysiological concentration (10−3 mol/L). The immobilization promoting effect of KYNA and the adhesion inducer activity of its derivatives indicate that these compounds could contribute to maintaining or restoring the protective function of brain endothelium; they also suggest that cell–ECM adhesion and related cell responses (e.g. migration/motility) could be potential new targets of KYNA.


Endothelial repair Kynurenic acid Holographic microscopy Impedimetry Synthetic kynurenines Brain endothelial cell Kynurenic acid (PubChem CID: 3845) l-Kynurenine (Pubchem CID: 161166) 



Authors express their gratitude to Auro-Science Consulting Kft for their expert technical assistance, and to Mr. P. Samotik and Mr. Z. Ambrus for proofreading and technical language support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Funding sources

This work was supported by the following grants: GINOP-2.3.2-15-2016-00034, MTA-SZTE Neuroscience Research Group. The funding sources were in no way involved in the conduct of the research, nor in the analysis or interpretation of data, nor in preparation of the article.

Supplementary material

702_2018_1839_MOESM1_ESM.pdf (575 kb)
Supplementary material 1 (PDF 575 kb)
702_2018_1839_MOESM2_ESM.pdf (337 kb)
Supplementary material 2 (PDF 338 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Genetics, Cell- and ImmunobiologySemmelweis UniversityBudapestHungary
  2. 2.MTA-SZTE Neuroscience Research GroupSzegedHungary
  3. 3.Institute of Pharmaceutical ChemistryUniversity of SzegedSzegedHungary
  4. 4.Stereochemistry Research Group of the Hungarian Academy of SciencesSzegedHungary
  5. 5.Institute of BiophysicsBiological Research Centre of the Hungarian Academy of SciencesSzegedHungary
  6. 6.Department of Physiology, Anatomy and NeuroscienceUniversity of SzegedSzegedHungary
  7. 7.Department of PharmacodynamicsSemmelweis UniversityBudapestHungary
  8. 8.Department of NeurologyUniversity of SzegedSzegedHungary

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