Kynurenic acid inhibits the electrical stimulation induced elevated pituitary adenylate cyclase-activating polypeptide expression in the TNC

Tamás Körtési, Bernadett Tuka, János Tajti, Teréz Bagoly, Ferenc Fülöp, Zsuzsanna Helyes, László Vécsei

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Migraine is a primary headache of imprecisely known mechanism, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Intensive research has recently focused on pituitary adenylate cyclase-activating polypeptide (PACAP) and the kynurenine systems as potential pathogenic factors. Aim: We investigated the link between these important mediators and the effects of kynurenic acid (KYNA) and its synthetic analog (KYNA-a) on PACAP expression in the rat trigeminal nucleus caudalis (TNC) in a TS stimulation model related to migraine mechanisms. Methods: Adult male Sprague-Dawley rats were pretreated with KYNA, KYNA-a, the NMDA receptor antagonist MK-801, or saline (vehicle). Next, the trigeminal ganglion (TRG) was electrically stimulated, the animals were transcardially perfused following 180 min, and the TNC was removed. In the TNC samples, 38 amino acid form of PACAP (PACAP1-38)-like radioimmunoactivity was measured by radioimmunoassay, the relative optical density of preproPACAP was assessed by Western blot analysis, and PACAP1-38 mRNA was detected by real-time PCR. Results and conclusion: Electrical TRG stimulation resulted in significant increases of PACAP1-38-LI, preproPACAP, and PACAP1-38 mRNA in the TNC. These increases were prevented by the pretreatments with KYNA, KYNA-a, and MK-801. This is the first study to provide evidence for a direct link between PACAP and the kynurenine system during TS activation.

Original languageEnglish
Article number745
JournalFrontiers in Neurology
Volume8
Issue numberJAN
DOIs
Publication statusPublished - Jan 16 2018

Keywords

  • Kynurenic acid
  • MK-801
  • Migraine
  • Pituitary adenylate cyclase-activating polypeptide
  • Trigeminovascular system

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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