Kynurenic acid and its analogue can alter the opioid receptor G-protein signaling after acute treatment via NMDA receptor in rat cortex and striatum

Reza Samavati, Ferenc Zádor, Edina Szűcs, Bernadett Tuka, Diána Martos, Gábor Veres, Róbert Gáspár, István M. Mándity, Ferenc Fülöp, László Vécsei, Sándor Benyhe, Anna Borsodi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Previously, we have shown that the N-methyl D-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor. The acute 30 minute in vivo KYNA1 and KYNA treatments altered opioid receptor G-protein signaling or ligand potency depending on the opioid receptor type and brain region (rat cortex vs striatum) using [35S]GTPγS binding assays. Pretreatment with the NMDA receptor antagonist MK-801 impaired or reversed the effects of KYNA1 and KYNA. These results suggest an NMDA receptor mediated effect. After acute 30 minute treatment HPLC measurements revealed a similar KYNA1 and a higher KYNA plasma concentration compared to cerebrospinal fluid concentrations. Finally, KYNA, KYNA1 and MK-801 showed comparable results in opioid receptor G-protein activity and ligand potency with acute in vivo treatments when they were administered in vitro for 30 min on isolated cortex and striatum slices. We previously demonstrated that KYNA1 and KYNA acutely altered opioid receptor function in vivo and in vitro through the NMDA receptor depending on the opioid receptor type and brain region. This study may lead to a new, indirect approach to influence opioid receptor signaling.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalJournal of the Neurological Sciences
Volume376
DOIs
Publication statusPublished - May 15 2017

Keywords

  • G-protein
  • KYNA
  • MK-801
  • Opioid receptor
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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