Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis

Gabor Csanyi, Béla Kis, Árpád Gecse, Gyula Telegdy, Zoltán Szupera, László Vécsei, Magdolna Szente, István Leprán, Zsófia Mezei

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1 Scopus citations

Abstract

We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [14C]AA as a tracer substrate and chromatographic determination. The recurrent epileptic seizures of male Wistar rats were induced every second day with 3-aminopyridine (3-AP, 25 mg/kg ip) for two weeks. In the chronic 3-AP model, the earlier epileptic insults resulted in a decreased incidence of limbic seizures and higher survival rate at later administration of 3-AP. After 3-AP treatment, the formation of lipoxygenase products was unchanged, but the total amount of cyclooxygenase (COX) metabolites was decreased both in platelets and brain microvessels. The reduction in COX-mediated eicosanoid synthesis after recurrent seizures was due to the decreased synthesis of vasodilator and vasoconstrictor COX metabolites. In platelets, the 3-AP-treatment reduced the synthesis of vasodilator prostacyclin (PGI2), prostaglandin E2 (PGE2) and 12-L-hydroxy-5,8, 10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D2 (PGD2) remained unchanged. In isolated brain capillaries, the PGD2, PGE2 and 12-HHT synthesis was decreased after recurrent seizures. As for the vasoconstrictor COX metabolites, both platelets and brain microvessels synthesized significantly lesser amount of prostaglandin F (PGF) and thromboxarie A2 (TxA2) upon 3-AP administration. Our results indicate that platelets and isolated brain capillaries synthesize significantly lesser amount of COX metabolites after chronic 3-AP treatment. The decreased conversion of AA into different COX products may play a role in the neuroprotective/preconditional adaptation of the brain against subsequent seizures.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalPharmacological Reports
Volume60
Issue number3
StatePublished - Aug 19 2008
Externally publishedYes

Keywords

  • 3-aminopyridine
  • Brain microvessels
  • Eicosanoids
  • Platelets
  • Prostaglandins
  • Seizure

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Csanyi, G., Kis, B., Gecse, Á., Telegdy, G., Szupera, Z., Vécsei, L., Szente, M., Leprán, I., & Mezei, Z. (2008). Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis. Pharmacological Reports, 60(3), 345-352.