Purchase this article with an account.
D. Yu, W.D. Eldred; Interactions of GABA and the NO/cGMP Signalling Pathway in the Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5146.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previous studies have determined that the nitric oxide (NO)/cGMP signal transduction pathway can be activated by excitatory amino acids such as NMDA or KA, but there is little information about the interactions of inhibitory transmitters like GABA and NO/cGMP. The present study was designed to test if blocking ionotropic GABA receptors can modulate NO/cGMP and if NO can modulate GABA levels in retina. Methods: To test the effects of GABA receptors, we used the GABA receptor antagonists bicuculline, picrotoxin, and TPMPA. Turtle eyecups were stimulated with the antagonists, and subsequently were fixed in 4% paraformaldehyde and stained using cGMP immunocytochemistry. To study the effects of NO on GABA release, isolated retinas were preloaded with a GABA analog, gamma-vinyl-GABA (GVG), before they were treated with the NO donor DETA NONOate, with or without the GABA transporter inhibitor nipecotic acid. Following fixation, these retinas were labeled using GVG immunocytochemistry. Results: Bicuculline strongly increased cGMP-like immunoreactivity (LI) in specific amacrine cells and their processes in the IPL, while picrotoxin showed moderate increases, and TPMPA produced only very low levels of cGMP–LI. Stimulations combining TPMPA and bicuculline yielded results similar to picrotoxin. Loading with GVG gave strong immunocytochemical labeling in GABAergic cells. NO donor decreased the GVG-LI in these cells, but nipecotic acid reduced this NO-stimulated decrease. Conclusions: In light-adapted retinas, basal GABAergic receptor activation inhibits the NO/cGMP signaling pathway, and NO donor stimulates transporter-mediated GABA release. Taken together, these results indicate that GABA inhibits NO production, which in turn inhibits NO-stimulated transporter-mediated GABA release. This relationship between GABA and NO/cGMP indicates that mutual feedback mechanisms regulate the NO/cGMP signal transduction pathway and GABA in retina.
This PDF is available to Subscribers Only