The synthesis of prostaglandins and thromboxane in the mouse brain in vivo

Abstract

The i.v. administration of convulsant doses of pentetrazole or picrotoxin induced an increase in PGF_2α, PGE₂ and TXB₂-like immunoreactive material in mouse brain tissue. The onset of increase coincided with the appearance of clonic seizures. The anticonvulsant drugs trimethadione and diazepam reduced both convulsions and increase of the above arachidonic acid metabolites induced by pentetrazole or picrotoxin. In synaptosomal preparations of the brain, neither pentetrazole (10⁻³ mol l⁻¹) picrotoxin (10⁻⁴ mol l⁻¹) nor trimethadione (5×10⁻⁴ mol l⁻¹) had any influence on cyclooxygenase activity as indicated by the unimpaired PGF_2α-synthesis. Under hypoxic conditions at equal durations as the seizures, the formation of PGF_2α and PGE₂ was less than 10% of the amount occurring after pentetrazole-induced convulsions. It is concluded that the seizure-induced rise of PGF_2α, PGE₂ and TXB₂ is the result of increased central nervous activity.