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W.D. Eldred, D. Yu; Nitric Oxide Stimulates Gaba Release And Inhibits Glycine Release In Retina . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4251.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Nitric oxide (NO) has been shown to modulate the uptake and/or release of neurotransmitters through a variety of mechanisms such as: activation of soluble guanylate cyclase (sGC) and cGMP–dependent mechanisms; reaction with superoxide O2– and subsequent oxidative reactions involving peroxynitrite (ONOO–); modulation of Ca2+ channels and Na+ channels; modulation of transporters; and direct modulation of synaptic vesicle docking molecules. In turtle retina, neuronal nitric oxide synthase (nNOS) has been associated with GABAergic and glycinergic amacrine cells. The goal of our study was to characterize the effects of NO on the release of GABA and glycine (GLY) and to examine the biochemical mechanisms involved. Methods: Using silver–intensified immunogold immunocytochemistry, we were able to monitor the changes in the levels of gamma–vinyl–GABA (GVG), a non–endogenous GABA analog, and GLY in the turtle retina in response to the following: a NO donor, DETA NONOate; the cGMP analog, 8–bromo–cGMP; a ONOO– donor, SIN 1; the GABA transporter inhibitor, nipecotic acid; Ca2+–free Ringer’s solution; high potassium Ringer’s solution; glutamate receptor antagonists; the GABAA receptor antagonist, bicuculline; a NOS inhibitor, SMTC; and/or the ONOO– scavenger, L–cysteine. Digital images were captured of the resultant immunocytochemical labeling seen with each treatment and the optical densities in comparable retinal regions were quantified. Results: We found that NO stimulates GVG release and inhibits glycine release. NO enhanced GVG release through both Ca2+–dependent and Ca2+–independent mechanisms, such as reversal of the GABA transporter, and through both cGMP and ONOO––mediated pathways. Effects due to the modulation of presynaptic transmitter release were involved for both GABA and glycine. Conclusions: These findings indicate that NO can increase GABA release and inhibit glycine release through different signaling pathways in specific retinal cell types.
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