Nitric oxide stimulates gamma-aminobutyric acid release and inhibits glycine release in retina.
Nitric oxide (NO) modulates the uptake and/or release of neurotransmitters through a variety of cellular mechanisms. However, the pharmacological and biochemical processes underlying these neurochemical effects of NO often remain unclear. In our study, we used immunocytochemical methods to study the effects of NO, cyclic guanosine monophosphate (cGMP), and peroxynitrite on the uptake and release of gamma-aminobutyric acid (GABA) and glycine in the turtle retina. In addition, we examined the involvement of glutamate receptors, calcium, and the GABA transporter in this GABA uptake and release. We also tested for interactions between the GABAergic and glycinergic systems. In general, we show that NO stimulated GABA release and inhibited glycine release. The NO-stimulated GABA release involved calcium-dependent or calcium-independent synaptic release or reversal of the GABA transporter. Some effects of NO on GABA release involved glutamate, cGMP, or peroxynitrite. NO promoted glycine uptake and inhibited its release, and this inhibition of glycine release was influenced by GABAergic modulation. These findings indicate that NO modulates the levels of the inhibitory transmitters GABA and glycine through several specific biochemical mechanisms in different retinal cell types and layers. Thus it appears that some of the previously described reciprocal interactions between GABA and glycine in the retina function through specific NO signaling pathways.
Yu
Dou
D
Department of Biology, Boston University, Boston, Massachusetts 02215, USA.
Eldred
William D
WD
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003671:DEET / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D016622:Silver Staining / Q000379:methods; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014426:Turtles; D020888:Vigabatrin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D018756:GABA Antagonists; D009557:Nipecotic Acids; D002104:Cadmium; D003671:DEET; C030278:nipecotic acid; D002956:Citrulline; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; C002385:linsidomine; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008981:Molsidomine; D020888:Vigabatrin; D013890:Thiourea; D006152:Cyclic GMP; C086717:S-methylthiocitrulline; D011188:Potassium; D005998:Glycine; D001640:Bicuculline