Inhibition of opioid receptor mediated G-protein activity after chronic administration of kynurenic acid and its derivative without direct binding to opioid receptors

Ferenc Zádor, Reza Samavati, Eszter Szlávicz, Bernadett Tuka, Engin Bojnik, F. Fülöp, J. Toldi, L. Vécsei, A. Borsodi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

There is an increasing number of evidence showing analgesic properties of the kynurenic acid (KYNA), and also some studies demonstrate that kynurenine might interact with the opioid system. Therefore in this study, for the first time we investigated the direct binding affinity of KYNA and its structural analog KYNA-1 towards mu, kappa and delta opioid receptor in competition binding experiments applying opioid receptor specific radioligands. The binding affinity measurements were performed in Chinese hamster ovary cell lines overexpressing the corresponding opioid receptor (mu and kappa opioid receptor were rat, delta opioid receptor were mouse sequence). Additionally we also examined the chronic effect of these compounds on mu, kappa and delta opioid receptor and also nociceptin peptide receptor mediated G-protein activity in [35S]GTPγS binding assays performed in mouse cortex and striatum membranes. Our results showed that KYNA and KYNA-1 had no affinity towards any of the three classic opioid receptors. On the other hand the compounds significantly decreased opioid and nociceptin receptor mediated G-protein activity or in some cases enhanced the potency of the activating ligand. Moreover, the alterations were receptor and brain region specific. Accordingly, we conclude that KYNA and KYNA-1 do not interact directly with the opioid receptors, but more likely alter the receptor functions intracellularly.

Original languageEnglish
Pages (from-to)1520-1529
Number of pages10
JournalCNS and Neurological Disorders - Drug Targets
Volume13
Issue number9
Publication statusPublished - Jan 1 2014

Fingerprint

Kynurenic Acid
Opioid Receptors
GTP-Binding Proteins
kappa Opioid Receptor
delta Opioid Receptor
mu Opioid Receptor
Kynurenine
Peptide Receptors
Cricetulus
Opioid Analgesics
Analgesics
Ovary
Ligands
Cell Line
Membranes
Brain

Keywords

  • G-protein
  • Kynurenic acid
  • Opioid receptors
  • Radioligand binding
  • [<sup>35</sup>S]GTPγS binding

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Inhibition of opioid receptor mediated G-protein activity after chronic administration of kynurenic acid and its derivative without direct binding to opioid receptors. / Zádor, Ferenc; Samavati, Reza; Szlávicz, Eszter; Tuka, Bernadett; Bojnik, Engin; Fülöp, F.; Toldi, J.; Vécsei, L.; Borsodi, A.

In: CNS and Neurological Disorders - Drug Targets, Vol. 13, No. 9, 01.01.2014, p. 1520-1529.

Research output: Contribution to journalArticle

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