NM  Vol.6 No.3 , September 2015
α,β-Methylene-ATP-Induced Inhibition of Acetylcholine Release on the Stellate Ganglion: Contribution of Nitric Oxide
In this study, we investigated the possible involvement of nitric oxide pathways in the presynaptic inhibition of acetylcholine release induced by ATP analogs in dogs. We performed the study using HPLC with electrochemical detection and the nitric oxide detection-HPLC system. The amount of acetylcholine released in response to preganglionic stimulation at 5 Hz for 10 min was reduced in a concentration-dependent manner after exposure to 10-7 - 10-4 M α,β-methylene-ATP (α,β-meATP), but not by the P2Y receptor agonist, 2-methyl-thio-ATP (2MeSATP) or the P2X1 receptor agonist, β,γ-methylene-ATP (β,γ-meATP), at the same concentrations. The inhibition of acetylcholine release induced by α,β-meATP was antagonized by: the nonselective P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2’,4’-disulphonic acid (PPADS); the P2X1, P2X3 and P2X2/3 receptors antagonist, 2’-(or-3’)-O-trinitrophenyl-ATP (TNP-ATP); the neuronal nitric oxide synthase (nNOS) inhibitor, 3-bromo-7-nitroindazole; the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ); the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethy-limidazoline-1-oxyl-3-oxide (carboxy-PTIO). Exposure to 10-5 M, but not 10-4 M, α,β-meATP, for 30 min increased the levels of , and this increase was antagonized by TNP-ATP and 3-bromo-7-nitroindazole. These results show that P2X receptor activation inhibits stellate ganglionic transmission by reducing acetylcholine release from presynaptic nerve terminals and that this inhibition seems to involve, at least in part, the activation of endogenous NO production and cGMP pathways.

Cite this paper
Kushiku, K. , Yamada, H. and Ono, N. (2015) α,β-Methylene-ATP-Induced Inhibition of Acetylcholine Release on the Stellate Ganglion: Contribution of Nitric Oxide. Neuroscience and Medicine, 6, 134-147. doi: 10.4236/nm.2015.63022.
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