当前位置： SCI文献检索 > JOURNAL OF THE NEUROLOGICAL SCIENCES期刊下所有文献 > Kynurenic acid and its analogue can alter the opioid receptor G-protein signaling after acute treatment via NMDA receptor in rat cortex and striatum.

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

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 30minute 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 30minute 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 30min 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.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Samavati R,Zádor F,Szűcs E,Tuka B,Martos D,Veres G,Gáspár R,Mándity IM,Fülöp F,Vécsei L,Benyhe S,Borsodi A

doi

10.1016/j.jns.2017.02.053

subject

Has Abstract

pub_date

2017-05-15 00:00:00

pages

63-70

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(17)30148-X

journal_volume

376

pub_type

杂志文章

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