Nitric oxide stimulates Ca(2+)-independent synaptic vesicle release.
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 KCl 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 Ca2+. Indo-1/AM measurements indicated that nitric oxide actually decreased intracellular Ca2+, and the Ca2+ channel blocker Cd2+ 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 Ca2+ and may provide an interesting new tool for the study of molecules involved in vesicle exocytosis.
Meffert
M K
MK
Department of Neurobiology, Stanford University School of Medicine, California 94305-5401.
Premack
B A
BA
Schulman
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005456:Fluorescent Dyes; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000502:physiology*; D007211:Indoles; D007700:Kinetics; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D012977:Sodium Nitrite / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
C073804:FM1 43; D005456:Fluorescent Dyes; D005971:Glutamates; D007211:Indoles; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D014665:Vasodilator Agents; C059587:Indo-1 pentaacetoxymethyl ester; D009599:Nitroprusside; D009569:Nitric Oxide; D018698:Glutamic Acid; C002385:linsidomine; D011189:Potassium Chloride; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D010396:Penicillamine; D012977:Sodium Nitrite; D002118:Calcium