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

Research output: Contribution to journalArticle

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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

Fingerprint

Eicosanoids
Prostaglandin-Endoperoxide Synthases
Seizures
Blood Platelets
Brain
Microvessels
Arachidonic Acid
Prostaglandin D2
Vasoconstrictor Agents
Epoprostenol
Vasodilator Agents
Dinoprostone
Epilepsy
Dinoprost
Lipoxygenase
varespladib methyl
3-aminopyridine
Wistar Rats
Incidence
12-hydroxy-5,8,10-heptadecatrienoic acid

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis. / Csanyi, Gabor; Kis, Béla; Gecse, Árpád; Telegdy, Gyula; Szupera, Zoltán; Vécsei, László; Szente, Magdolna; Leprán, István; Mezei, Zsófia.

In: Pharmacological Reports, Vol. 60, No. 3, 19.08.2008, p. 345-352.

Research output: Contribution to journalArticle

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, vol. 60, no. 3, pp. 345-352.
Csanyi G, Kis B, Gecse Á, Telegdy G, Szupera Z, Vécsei L et al. Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis. Pharmacological Reports. 2008 Aug 19;60(3):345-352.
Csanyi, Gabor ; Kis, Béla ; Gecse, Árpád ; Telegdy, Gyula ; Szupera, Zoltán ; Vécsei, László ; Szente, Magdolna ; Leprán, István ; Mezei, Zsófia. / Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis. In: Pharmacological Reports. 2008 ; Vol. 60, No. 3. pp. 345-352.
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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 F2α (PGF2α) 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.",
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AU - Szupera, Zoltán

AU - Vécsei, László

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