Prostaglandin F2 alpha synthesis in the hippocampal mossy fiber synaptosomal preparation: I. Dependence in arachidonic acid, phospholipase A2, calcium availability and membrane depolarization.

Isolated hippocampal mossy fiber synaptosomes were used to characterize control mechanisms of prostaglandin F2 alpha (PGF2 alpha) synthesis at a central mammalian synapse. Exogenous arachidonic acid stimulated the dose-dependent synthesis of PGF2 alpha, as did the addition of phospholipase A2 or the activation of endogenous phospholipase A2. Phospholipase A2 inhibitors attenuated prostaglandin synthesis, but phospholipase C inhibitors had no effect. However, a diglyceride kinase inhibitor reduced PGF2 alpha accumulation. The cyclooxygenase inhibitor ibuprofen eliminated PGF2 alpha production, while the lipoxygenase inhibitors baicalein and NDGA reduced PGF2 alpha accumulation. The CA(2+)-ionophore-dependent stimulation of PGF2 alpha synthesis was abolished by Cd2+ or Ni2+. Further more, PGF2 alpha production appeared to be dependent on Ca2+ influx via L-type, but not N- or T-type, voltage-sensitive Ca2+ channels. Membrane depolarization with KC1, veratridine or 4-aminopyridine stimulated the synthesis of PGF2 alpha. This depolarization-dependent stimulation of PGF2 alpha synthesis was attenuated by L-type voltage-sensitive Ca2+ channel blockers, phospholipase A2 inhibitors, a K+ channel activator and a Na+ channel blocker. The activation of protein kinase C also led to a reduction of PGF2 alpha accumulation in depolarized nerve endings. These results may be used to suggest that PGF2 alpha production by hippocampal mossy fiber synaptosomes was controlled by the Ca(2+)- and phospholipase A2-dependent accumulation of unesterified arachidonic acid and was modulated by membrane depolarization and the activity of protein kinase C.