Glutamate exocytosis evoked by 4-aminopyridine is inhibited by free fatty acids released from rat cerebrocortical synaptosomes

Abstract

The Ca 2+-dependent release of glutamate induced by 4-aminopyridine (4-AP) in rat cerebral cortical synaptosomes was reduced by removal of bovine serum albumin (BSA) from the incubation medium. The decrease in the glutamate release in the absence of BSA was consistent with a reduction in the rise in cytosolic free [Ca 2+] after depolarization with 4-AP. Contrarily, neither the glutamate release nor the elevation in cytosolic free [Ca 2+] after depolarization with 30 mM KCl was altered by the removal of BSA. The inhibitory action of the free fatty acids released during the incubation of synaptosomes was also observed when exogenous free fatty acids were added to the medium in the presence of BSA. The highest inhibition of 4-AP-induced release of glutamate was observed in the presence of arachidonic acid. The results strongly suggest an inhibitory action of free fatty acids by decreasing Ca 2+ entry and glutamate release in rat cerebrocortical synaptosomes.