NITRIC-OXIDE STIMULATES CA2-INDEPENDENT SYNAPTIC VESICLE RELEASE()

A new fluorescence method using the dye FM1-43 was used to examine exo cytotic release from hippocampal synaptosomes. Nitric oxide caused a m arked transient stimulation of vesicle release. Several structurally u nrelated nitric oxide donors, sodium nitroprusside, S-nitroso-N-acetyl penicillamine, 3-morpholino-sydnonimine, and acidified sodium nitrite, were effective. Release stimulated by nitric oxide and KCl were compa rable in time course, using both the fluorescence assay and [H-3]L-glu tamate to monitor neurotransmitter release. Activation of guanylyl: cy clase was not responsible for nitric oxide-stimulated release. Unlike release stimulated by KCl or A23187, nitric oxide-stimulated release w as found to be independent of a rise in intrasynaptosomal Ca2+. Indo-1 /AM measurements indicated that nitric oxide actually decreased intrac ellular Ca2+, and the Ca2+ channel blocker Cd2+ did not affect nitric oxide-stimulated vesicle release. Nitric oxide does, however, appear t o act on the Ca2+-sensitive pool of vesicles. Nitric oxide may be the first physiological mediator that induces vesicle exocytosis without r aising Ca2+ and may provide an interesting new tool for the study of m olecules involved in vesicle exocytosis.