title: Neomycin inhibits K+- and veratridine-stimulated noradrenaline release in rat brain slices and rat brain synaptosomes.
abstract: 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 phosphoinositides, which is necessary for Ca2+ mobilization, participates in the Ca2+-dependent induced neurotransmitter release in the central nervous system.
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
chemical_list: D014701:Veratridine; D014702:Veratrine; D009355:Neomycin; D011188:Potassium; D009638:Norepinephrine