Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis
We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [C-14]AA as a tracer substrate and chromatographic determination. The recurrent epileptic seizures of male Wistar rats were induced every second day with 3-am...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2008
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| Sorozat: | PHARMACOLOGICAL REPORTS
60 No. 3 |
| mtmt: | 1168144 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9967 |
| Tartalmi kivonat: | We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [C-14]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 (PGI(2)), prostaglandin E-2 (PGE(2)) and 12-L-hydroxy5,8, 10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D-2 (PGD(2)) 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-2 alpha, (PGF(2 alpha)) and thromboxane A(2) (TxA(2)) 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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| Terjedelem/Fizikai jellemzők: | 345-352 |
| ISSN: | 1734-1140 |