Nitric oxide stimulates Ca(2+)-independent synaptic vesicle release

Neuron. 1994 Jun;12(6):1235-44. 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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Fluorescent Dyes
  • Glutamates / metabolism
  • Glutamic Acid
  • Hippocampus / physiology*
  • Indoles
  • Kinetics
  • Male
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • Nitric Oxide / pharmacology*
  • Nitroprusside / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Potassium Chloride / pharmacology
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Rats
  • Rats, Sprague-Dawley
  • S-Nitroso-N-Acetylpenicillamine
  • Sodium Nitrite / pharmacology
  • Spectrometry, Fluorescence
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology*
  • Vasodilator Agents / pharmacology


  • FM1 43
  • Fluorescent Dyes
  • Glutamates
  • Indoles
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Vasodilator Agents
  • Indo-1 pentaacetoxymethyl ester
  • Nitroprusside
  • Nitric Oxide
  • Glutamic Acid
  • linsidomine
  • Potassium Chloride
  • S-Nitroso-N-Acetylpenicillamine
  • Molsidomine
  • Penicillamine
  • Sodium Nitrite
  • Calcium