Neomycin inhibits K⁺ - and veratridine-stimulated noradrenaline release in rat brain slices and rat brain synaptosomes

The possible involvement of phosphoinositides' turnover in the process of neurotransmitter release in the central nervous system (CNS) was studied using rat brain slices and synaptosomes. A depolarizing concentration of potassium chloride (25 mM) induces an 8.6 ± 0.4% increase of [³H]noradrenaline ([³H]NA) fractional release in cerebral cortical slices above spontaneous release, and 15 mM KCl induces a 3-fold increase of [³H]NA release in rat brain synaptosomes. Neomycin, an aminoglycoside which binds phosphoinositides, inhibits the potassium-induced release in cortical slices with an IC₅₀ = 0.5 ± 0.07 mM and with IC₅₀ = 0.2 ± 0.03 mM in synaptosomes. Veratridine, a veratrum alkaloid which increases membrane permeability to sodium ions and causes depolarization of neuronal cells, induces a net 13.4 ± 0.3% increase of [³H]NA fractional release above spontaneous release in cortical slices. In analogy to K⁺ stimulation, neomycin inhibits the veratridine-stimulated release in cortical slices with an IC₅₀ = 0.65 ± 0.1 mM. It appears that the recycling of phospoinositides, which is necessary for Ca²⁺ mobilization, participates in the Ca²⁺-dependent induced neurotransmitter release in the central nervous system.