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Kynurenic acid synthesis in bovine retinal slices – effect of glutamate agonists

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Summary.

The purpose of the present study was to investigate the effect of glutamate agonists upon kynurenic acid (KYNA) production in bovine retinal slices. Quantitative analysis of newly synthesized KYNA was carried out using an HPLC system and detected fluorimetrically. Glutamate at the concentration of 0.01, 0.1 and 1 mM reduced KYNA synthesis in the retinal slices to 70% (p < 0.05), 35% (p < 0.01) and 23% (p < 0.001), respectively. The concentration of glutamate reducing production of KYNA by 50% (IC50) was 0.035 mM (0.02–0.06). Aspartate at the concentration of 0.01, 0.1 and 1 mM lowered KYNA synthesis in the retinal slices to 80% (p < 0.01), 57% (p < 0.001) and 43% (p < 0.001), respectively. In contrast, kainic acid (up to 5 mM), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (up to 1 mM) and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) (up to 3 mM) turned out to be ineffective in diminishing KYNA synthesis. These data demonstrate that glutamate, aspartate and N-methyl-D-aspartate (NMDA) inhibit KYNA synthesis in bovine retinal slices with different potency.

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Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

EAA:

excitatory amino acid

HPLC:

high performance liquid chromatography

KA:

kainic acid

KAT:

kynurenine aminotransferase

KYNA:

kynurenic acid

NMDA:

N-methyl-D-aspartate

t-ACPD:

1-aminocyclopentane-trans-1,3-dicarboxylic acid

References

  • R Carpenedo A Pittaluga A Cozzi S Attucci A Galli M Raiteri F Moroni (2001) ArticleTitlePresynaptic kynurenate-sensitive receptors inhibit glutamate release Eur J Neurosci 13 2141–2147 Occurrence Handle11422455 Occurrence Handle1:STN:280:DC%2BD3Mzmt1WqsA%3D%3D Occurrence Handle10.1046/j.0953-816x.2001.01592.x

    Article  PubMed  CAS  Google Scholar 

  • L Curatalo C Caccia C Speciale L Raimondi M Cini M Marconi A Molinari R Schwarcz (1996) ArticleTitleModulation of extracellular kynurenic acid content by excitatory amino acids in primary cultures of rat astrocytes Adv Exp Med Biol 398 273–276

    Google Scholar 

  • U Gerber (2003) ArticleTitleMetabotropic glutamate receptors in vertebrate retina Doc Ophthalmol 106 83–87 Occurrence Handle12675489 Occurrence Handle10.1023/A:1022477203420

    Article  PubMed  Google Scholar 

  • JBP Gramsbergen PS Hodgkins A Rassoulpour WA Turski P Guidetti R Schwarcz (1997) ArticleTitleBrain-specific modulation of kynurenic acid synthesis in the rat J Neurochem 69 290–298 Occurrence Handle9202322 Occurrence Handle1:CAS:528:DyaK2sXktV2msL8%3D Occurrence Handle10.1046/j.1471-4159.1997.69010290.x

    Article  PubMed  CAS  Google Scholar 

  • T Grunder K Kohler A Kaletta E Günther (2000) ArticleTitleThe distribution and developmental regulation of NMDA receptor subunit proteins in the outer and inner retina of the rat J Neurobiol 44 333–342 Occurrence Handle10942886 Occurrence Handle1:CAS:528:DC%2BD3cXmsVSgtrg%3D Occurrence Handle10.1002/1097-4695(20000905)44:3<333::AID-NEU4>3.0.CO;2-S

    Article  PubMed  CAS  Google Scholar 

  • P Guidetti E Okuno R Schwarcz (1997) ArticleTitleCharacterization of rat brain kynurenine aminotransferases I and II J Neurosci Res 50 457–465 Occurrence Handle9364331 Occurrence Handle1:CAS:528:DyaK2sXnt1entr0%3D Occurrence Handle10.1002/(SICI)1097-4547(19971101)50:3<457::AID-JNR12>3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

  • MF Haberecht DA Redburn (1996) ArticleTitleHigh levels of extracellular glutamate are present in retina during neonatal development Neurochem Res 21 285–291 Occurrence Handle9182254 Occurrence Handle1:CAS:528:DyaK28XivFers7w%3D

    PubMed  CAS  Google Scholar 

  • C Hilmas EF Pereira M Alkondon A Rassoulpour R Schwarcz EX Albuquerque (2001) ArticleTitleThe brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications J Neurosci 21 7463–7473 Occurrence Handle11567036 Occurrence Handle1:CAS:528:DC%2BD3MXnsFCksrc%3D

    PubMed  CAS  Google Scholar 

  • PS Hodgkins R Schwarcz (1998) ArticleTitleMetabolic control of kynurenic acid formation in the rat brain Dev Neurosci 20 408–416 Occurrence Handle9778579 Occurrence Handle1:CAS:528:DyaK1cXntl2ltr0%3D Occurrence Handle10.1159/000017338

    Article  PubMed  CAS  Google Scholar 

  • T Kocki M Dolinska A Dybel EM Urbanska WA Turski J Albrecht (2002) ArticleTitleRegulation of kynurenic acid synthesis in C6 glioma cells J Neurosci Res 68 622–626 Occurrence Handle12111852 Occurrence Handle1:CAS:528:DC%2BD38Xks1Kqu7g%3D Occurrence Handle10.1002/jnr.10243

    Article  PubMed  CAS  Google Scholar 

  • T Kocki P Luchowski E Luchowska M Wielosz WA Turski EM Urbanska (2003) ArticleTitleL-cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II Neurosci Lett 346 97–100 Occurrence Handle12850557 Occurrence Handle1:CAS:528:DC%2BD3sXltF2gt7g%3D Occurrence Handle10.1016/S0304-3940(03)00579-2

    Article  PubMed  CAS  Google Scholar 

  • DM Linn SC Massey (1996) ArticleTitleHomocysteate-evoked release of acetylcholine from the rabbit retina J Neurochem 66 153–160 Occurrence Handle8522948 Occurrence Handle1:CAS:528:DyaK2MXhtVSns7vL Occurrence Handle10.1046/j.1471-4159.1996.66010153.x

    Article  PubMed  CAS  Google Scholar 

  • E Luchowska P Luchowski R Paczek A Ziembowicz T Kocki WA Turski M Wielosz J Lazarewicz EM Urbanska (2004) ArticleTitleDual effect of DL-homocysteine and S-adenosyl-homocysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acid J Neurosci Res 79 375–385 Occurrence Handle10.1002/jnr.20359 Occurrence Handle1:CAS:528:DC%2BD2MXhtVWgu7Y%3D

    Article  CAS  Google Scholar 

  • P Moore A El-Sherbeny P Roon PV Schoenlein V Ganapathy SB Smith (2001) ArticleTitleApoptotic cell death in the mouse retinal ganglion cell layer is induced in vivo by the excitatory amino acid homocysteine Exp Eye Res 73 45–57 Occurrence Handle11428862 Occurrence Handle1:CAS:528:DC%2BD3MXks1Orsrg%3D Occurrence Handle10.1006/exer.2001.1009

    Article  PubMed  CAS  Google Scholar 

  • F Moroni P Russi G Lombardi M Beni V Carla (1988) ArticleTitlePresence of kynurenic acid in the mammalian brain J Neurochem 51 177–180 Occurrence Handle3379401 Occurrence Handle1:CAS:528:DyaL1cXksVyqtLk%3D

    PubMed  CAS  Google Scholar 

  • MN Perkins TW Stone (1982) ArticleTitleAn iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid Brain Res 247 184–187 Occurrence Handle6215086 Occurrence Handle1:CAS:528:DyaL38Xls1Slsr4%3D Occurrence Handle10.1016/0006-8993(82)91048-4

    Article  PubMed  CAS  Google Scholar 

  • B Poeggeler A Rassoulpour P Guidetti HQ Wu R Schwarcz (1998) ArticleTitleDopaminergic control of kynurenate levels and N-methyl-D-aspartate toxicity in the developing rat striatum Dev Neurosci 20 146–153 Occurrence Handle9691189 Occurrence Handle1:CAS:528:DyaK1cXltVGnsrk%3D Occurrence Handle10.1159/000017309

    Article  PubMed  CAS  Google Scholar 

  • R Rejdak T Zarnowski WA Turski T Kocki Z Zagórski E Günther K Kohler E Zrenner (2002) ArticleTitleChanges of kynurenic acid content in the rat and chicken retina during ontogeny Graefes Arch Clin Exp Ophthalmol 240 687–691 Occurrence Handle12192464 Occurrence Handle1:CAS:528:DC%2BD38XotVSmsLc%3D

    PubMed  CAS  Google Scholar 

  • R Rejdak T Żarnowski WA Turski T Kocki Z Zagórski E Zrenner F Schuettauf (2003) ArticleTitleAlterations of kynurenic acid content in the retina in response to retinal ganglion cell damage Vision Res 43 497–503 Occurrence Handle12594996 Occurrence Handle1:CAS:528:DC%2BD3sXht1CrsLc%3D Occurrence Handle10.1016/S0042-6989(02)00682-X

    Article  PubMed  CAS  Google Scholar 

  • R Rejdak T Żarnowski WA Turski E Okuno T Kocki Z Zagórski K Kohler E Günther E Zrenner (2001) ArticleTitlePresence of kynurenic acid and kynurenine aminotransferases in the inner retina Neuroreport 12 3675–3678 Occurrence Handle11726772 Occurrence Handle1:CAS:528:DC%2BD3MXpt1Grs7k%3D Occurrence Handle10.1097/00001756-200112040-00014

    Article  PubMed  CAS  Google Scholar 

  • R Shibata (1988) ArticleTitleFluorimetric microdeterminations of kynurenic acid, an endogenous blocker of neurotoxicity, by high-performance liquid chromatography J Chromatogr 430 376–380 Occurrence Handle3235510 Occurrence Handle1:CAS:528:DyaL1cXls1eltr0%3D

    PubMed  CAS  Google Scholar 

  • TW Stone (1993) ArticleTitleNeuropharmacology of quinolinic and kynurenic acid Pharmacol Rev 45 309–379 Occurrence Handle8248282 Occurrence Handle1:CAS:528:DyaK3sXmtFKltr8%3D

    PubMed  CAS  Google Scholar 

  • WA Turski JBP Gramsbergen H Traitler R Schwarcz (1989) ArticleTitleRat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine J Neurochem 52 1629–1636 Occurrence Handle2709016 Occurrence Handle1:CAS:528:DyaL1MXitVKnsbY%3D

    PubMed  CAS  Google Scholar 

  • WA Turski M Nakamura WP Todd BK Carpenter WO Whetsell R Schwarcz (1988) ArticleTitleIdentification and quantification of kynurenic acid in human brain tissue Brain Res 545 164–169 Occurrence Handle10.1016/0006-8993(88)90815-3

    Article  Google Scholar 

  • WA Turski R Schwarcz (1988) ArticleTitleOn the disposition of intrahippocampally injected kynurenic acid in the rat Exp Brain Res 71 563–567 Occurrence Handle3416969 Occurrence Handle1:CAS:528:DyaL1cXlsVajsr8%3D Occurrence Handle10.1007/BF00248748

    Article  PubMed  CAS  Google Scholar 

  • E Urbańska T Kocki T Saran Z Kleinrok WA Turski (1997) ArticleTitleImpairment of brain kynurenic acid production by glutamate metabotropic receptor agonists Neuroreport 8 3501–3505 Occurrence Handle9427315 Occurrence Handle10.1097/00001756-199711100-00017

    Article  PubMed  Google Scholar 

  • EM Urbańska M Chmielewski T Kocki WA Turski (2000) ArticleTitleFormation of endogenous glutamatergic receptors antagonist kynurenic acid – differences between cortical and spinal cord slices Brain Res 878 210–212 Occurrence Handle10996154 Occurrence Handle10.1016/S0006-8993(00)02704-9

    Article  PubMed  Google Scholar 

  • K Wejksza W Rzeski J Parada-Turska B Zdzisińska R Rejdak T Kocki E Okuno M Kandefer-Szerszen E Zrenner WA Turski (2004) ArticleTitleKynurenic acid production in cultured bovine aortic endothelial cells. Homocysteine is a potent inhibitor Naunyn Schmiedebergs Arch Pharmacol 369 300–304 Occurrence Handle14770276 Occurrence Handle1:CAS:528:DC%2BD2cXhvFCnurg%3D Occurrence Handle10.1007/s00210-004-0872-2

    Article  PubMed  CAS  Google Scholar 

  • D Zhang SA Lipton (1992) ArticleTitleL-homocysteic acid selectively activates N-methyl-D-aspartate receptors of rat retinal ganglion cells Neurosci Lett 25 173–177 Occurrence Handle10.1016/0304-3940(92)90545-I

    Article  Google Scholar 

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Authors and Affiliations

  1. Tadeusz Krwawicz Chair of Ophthalmology and 1st Eye Hospital, Poland

    T. Zarnowski, R. Rejdak & Z. Zagorski

  2. Department of Patophysiology, Medical University of Lublin, Poland

    M. Bialek

  3. Department of Pathophysiology of Vision and Neuro-Ophthalomology, University Eye Hospital Tuebingen, Germany

    R. Rejdak & E. Zrenner

  4. Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    R. Rejdak

  5. Department of Ophthalmology, University of Erlangen-Nürnberg, Germany

    A. Junemann

  6. Department of Pharmacology and Toxicology, Medical University, Lublin, Poland

    T. Kocki & W. A. Turski

  7. Department of Toxicology, Institute of Agricultural Medicine, Lublin, Poland

    W. A. Turski

Authors
  1. T. Zarnowski
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  2. M. Bialek
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  3. R. Rejdak
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  4. E. Zrenner
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  5. A. Junemann
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  6. Z. Zagorski
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  7. T. Kocki
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  8. W. A. Turski
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Zarnowski, T., Bialek, M., Rejdak, R. et al. Kynurenic acid synthesis in bovine retinal slices – effect of glutamate agonists. J Neural Transm 113, 1367–1372 (2006). https://doi.org/10.1007/s00702-005-0423-0

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  • DOI: https://doi.org/10.1007/s00702-005-0423-0

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