Structure-function relationships for kynurenic acid analogues at excitatory pathways in the rat hippocampal slice

Michael B. Robinson, Marvin K. Schulte, Ronald K. Freund, Rodney L. Johnson, James F. Koerner

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Eight kynurenic acid analogues were bath-applied to rat hippocampal slices while recording extracellular synaptic field potentials and the potencies of these analogues for inhibition of these responses were compared to that of kynurenic acid. Quinaldic acid, 4-hydroxyquinoline, 4-hydroxypicolinic acid, l-kynurenine and picolinic acid inhibited evoked field potentials, but were at least 15-fold less potent than kynurenic acid in all pathways tested. Xanthurenic acid was inactive in the pathways tested. Quinolinic acid and dipicolinic acid showed signs of agonist activity with IC50's of approx. 400 μM and 2500 μM, respectively. These studies show that the 2-carboxy group and the 4-hydroxy moiety are essential for the antagonist activity exhibited by kynurenate. They also show that the unsubstituted second aromatic ring greatly enhances the affinity of kynurenate for these receptors and that substitution in at least one position on this aromatic ring abolishes activity.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalBrain Research
Volume361
Issue number1-2
DOIs
StatePublished - Dec 30 1985

Keywords

  • excitatory amino acid
  • extracellular recording
  • function relationship
  • glutamate analogue
  • hippocampal slice
  • kynurenic acid analogue
  • structure

Fingerprint Dive into the research topics of 'Structure-function relationships for kynurenic acid analogues at excitatory pathways in the rat hippocampal slice'. Together they form a unique fingerprint.

Cite this