Nitric oxide stimulates Ca 2+-independent synaptic vesicle release

• Published in: Neuron (Cambridge, Mass.) Vol. 12; no. 6; pp. 1235 - 1244
• Main Authors: Meffert, Mollie K., Premack, Brett A., Schulman, Howard
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 1994
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/0896-6273(94)90440-5

A new fluorescence method using the dye FM1-43 was used to examine exocytotic release from hippocampal synaptosomes. Nitric oxide caused a marked transient stimulation of vesicle release. Several structurally unrelated nitric oxide donors, sodium nitroprusside, S-nitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine, and acidified sodium nitrite, were effective. Release stimulated by nitric oxide and KCI were comparable in time course, using both the fluorescence assay and [ 3H] l-glutamate to monitor neurotransmitter release. Activation of guanylyl cyclase was not responsible for nitric oxide-stimulated release. Unlike release stimulated by KCl or A23187, nitric oxide-stimulated release was found to be independent of a rise in intrasynaptosomal Ca 2+. Indo-1/AM measurements indicated that nitric oxide actually decreased intracellular Ca 2+, and the Ca 2+ channel blocker Cd 2+ did not affect nitric oxide-stimulated vesicle release. Nitric oxide does, however, appear to act on the Ca 2+-sensitive pool of vesicles. Nitric oxide may be the first physiological mediator that induces vesicle exocytosis without raising Ca 2+ and may provide an interesting new tool for the study of molecules involved in vesicle exocytosis.