Role of acetylcholine in nitric oxide production in the salamander retina

Abstract

Although acetylcholine is one of the most widely studied neurotransmitters in the retina, many questions remain about its downstream signaling mechanisms. In this study we initially characterized the cholinergic neurotransmitter system in the salamander retina by localizing a variety of cholinergic markers. We then examined the link between both muscarinic and nicotinic receptor activation and nitric oxide production by using immunocytochemistry for cyclic guanosine monophosphate (cGMP) as an indicator. We found a large increase in cGMP-like immunoreactivity (cGMP-LI) in the inner retina in response to muscarinic (but not nicotinic) receptor activation. Based on the amplification of mRNA transcripts, receptor immunocytochemistry, and the use of selective antagonists, we identified these receptors as M2 muscarinic receptors. Using double-labeling techniques, we established that these increases in cGMP-LI were seen in GABAergic but not cholinergic amacrine cells, and that the increases were blocked by inhibitors of nitric oxide production. The creation of nitric oxide in response to cholinergic receptor activation may provide a mechanism for modulating the well-known mutual interactions of acetylcholine-glycine-GABA in the inner retina. As GABA and glycine are the primary inhibitory neurotransmitters in the retina, signaling pathways that modulate their levels or release will have major implications for the processing of complex stimuli by the retina.

Nitric Oxide (NO) Mediates the Inhibition of Form-Deprivation Myopia by Atropine in Chicks

“…Additionally, the evidence for direct interaction between ACh and modulation of NOS in the retina is sparse and conflicting. For example, oxotremorine increases immunoreactive cGMP via mAChR M2 in salamander retina 35 , but via mAChR M1/M3 in rat 36 ; and while induction of nitric oxide enhances light-evoked release of ACh from amacrine cells in the rabbit 37 , it inhibits high K + -evoked release of ACh in the rat 38 . In the chick, no studies such as these have been published.…”

IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

“…However, in salamander retina Cimini and co-workers demonstrated the co-localization of M2 mAChRs and ChAT (Cimini et al 2008). These contradictory results could be explained by the differences between the two species studied.…”

Inhibition of nitric oxide synthase desensitizes retinal ganglion cells to light by diminishing their excitatory synaptic currents under light adaptation

“…The effects of L-NAME were observed after a perfusion time of 10 minutes and continued throughout the duration of the L-NAME perfusion for each of the L-NAME experiments (Li & Hatton, 2000). L-NAME, a NOS inhibitor, has been shown to decrease endogenous NO in the retina (Cimini, Strang, Wotring, Keyser & Eldred, 2008, Kono, Chisato, Ebisawa, Asama, Sugawara, Ayabe, Kohgo, Kasai, Yoneda & Takahashi, 2004). …”