The inimitable kynurenic acid: The roles of different ionotropic receptors in the action of kynurenic acid at a spinal level

Gabor Tuboly, Lilla Tar, Zsuzsanna Bohar, Arpad Safrany-Fark, Zita Petrovszki, G. Kékesi, L. Vécsei, A. Párdutz, G. Horváth

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Kynurenic acid (KYNA) is a neuroactive metabolite that interacts with NMDA, AMPA/kainate and alpha 7 nicotinic receptors. The goal of this study was to clarify the roles of these receptors in the action of KYNA at a spinal level by using highly specific receptor antagonists alone or in triple combinations.Chronic osteoarthritis-like joint pain was induced with monosodium-iodoacetate in male Wistar rats. Mechanical allodynia and motor function were quantified. In the first series we determined the dose-response and time course effects of intrathecally administered KYNA (10-100. μg), d-(-)-2-amino-5-phosphonopentanoic acid (AP5; an NMDA receptor antagonist; 10-200. μg), methyllycaconitine (MLA; an alpha 7 nicotinic receptor antagonist; 100-200. μg) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulfonamide (NBQX; an AMPA/kainate receptor antagonist; 1-20. μg). In the second series, four different triple combinations of MLA, AP5 and NBQX were investigated.Intrathecal administration of KYNA caused a dose-dependent motor impairment and antinociception. The highly specific NMDA receptor antagonist AP5 caused a motor impairment and antinociception with lower potency. High doses of NBQX resulted in significant antinociception with a slight motor impairment, while only the highest dose of MLA gave rise to significant antinociception with a slight motor impairment. After the coadministration of these ligands as combinations, no potentiation was observed. It may be supposed that the effects of KYNA are primarily due to the inhibition of NMDA receptors at both glycine and phencyclidine (PCP) binding sites, and not to the interactions at the different ionotropic receptors, but the mechanisms behind its high bio-efficiency are still unknown.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalBrain Research Bulletin
Volume112
DOIs
Publication statusPublished - Mar 1 2015

Fingerprint

Kynurenic Acid
N-Methyl-D-Aspartate Receptors
Nicotinic Receptors
Nicotinic Antagonists
Iodoacetates
2-Amino-5-phosphonovalerate
Kainic Acid Receptors
Phencyclidine
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Kainic Acid
Hyperalgesia
Sulfonamides
Arthralgia
N-Methylaspartate
Osteoarthritis
Glycine
Reaction Time
Wistar Rats
Binding Sites

Keywords

  • Glutamate receptors
  • Interaction
  • Kynurenic acid
  • Pain
  • Spinal anesthesia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The inimitable kynurenic acid : The roles of different ionotropic receptors in the action of kynurenic acid at a spinal level. / Tuboly, Gabor; Tar, Lilla; Bohar, Zsuzsanna; Safrany-Fark, Arpad; Petrovszki, Zita; Kékesi, G.; Vécsei, L.; Párdutz, A.; Horváth, G.

In: Brain Research Bulletin, Vol. 112, 01.03.2015, p. 52-60.

Research output: Contribution to journalArticle

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