Characterization of seizure-induced cysteinyl-leukotriene formation in brain tissue of convulsion-prone gerbils.
Tonic-clonic seizures elicited in convulsion-prone gerbils resulted in a large increase in immunoreactive prostaglandin (PG) F2 alpha and in a smaller increase in immunoreactive leukotriene (LT) C4-like material in brain tissue. Brain tissue contents of both eicosanoids were found to reach a maximum at 6 min after the onset of seizures and were still elevated at 54 min after the beginning of convulsions. By reversed phase HPLC the immunoreactive LTC4-like material was identified as LTC4 and LTD4 at 6 min after the onset of convulsions, whereas at 54 min after the onset, transformation of LTD4 to LTE4 could be detected as well. In gerbils showing only weak seizure activity a small increase in PGF2 alpha but no increase in immunoreactive LTC4-like material could be detected at 6 min after the onset of convulsions. Pretreatment with indomethacin abolished the formation of PGF2 alpha but significantly enhanced the biosynthesis of immunoreactive LTC4-like material at 18 min after the beginning of seizures. The results demonstrate formation of cysteinyl-LT following tonic-clonic convulsions in spontaneously convulsing gerbils which could be enhanced by inhibition of the cyclooxygenase pathway of arachidonic acid metabolism. Since cysteinyl-LT have potent biological actions in various organs this finding warrants further investigations on the potential role of cysteinyl-LT in the CNS.
Simmet
T
T
Department of Pharmacology and Toxicology, Ruhr University, Bochum, F.R.G.
Seregi
A
A
Hertting
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost; D005260:Female; D005849:Gerbillinae / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D017999:Leukotriene E4; D008297:Male; D011460:Prostaglandins F / Q000096:biosynthesis; D013189:SRS-A / Q000031:analogs & derivatives / Q000096:biosynthesis*; D012640:Seizures / Q000378:metabolism*
D011460:Prostaglandins F; D013189:SRS-A; D017999:Leukotriene E4; D015237:Dinoprost; D007213:Indomethacin