Exogenous nitric oxide causes collapse of retinal ganglion cell axonal growth cones in vitro.
We show that nitric oxide (NO) from applied NO-donating chemicals induces collapse of ganglion cell axonal growth cones extending from explants of tadpole retina in culture. Peroxynitrite, a neurotoxic product of NO and superoxide reaction, did not induce collapse, and oxyhemoglobin, which binds NO, blocked the highly effective collapsing activity of the NO donor S-nitrosocysteine. Membrane-permeable analogs of cyclic guanosine monophosphate had no collapsing activity. Inhibitors of NO synthase did not induce collapse. NO is a potential retrograde messenger through which postsynaptic neurons signal to their inputs to modify synaptic efficacy following NMDA receptor activation. Our results suggest a role for NO as such a messenger during development of the retinotectal projection.
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Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520-8103, USA.
Constantine-Paton
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D000818:Animals; D001369:Axons / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D003545:Cysteine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008623:Mercaptoethanol; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D015398:Signal Transduction / Q000502:physiology; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D014982:Xenopus laevis
D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013439:Sulfhydryl Reagents; D014665:Vasodilator Agents; D009599:Nitroprusside; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D010396:Penicillamine; D003545:Cysteine