Potentiation of nicotinic transmission in the rat superior cervical sympathetic ganglion: effects of cyclic GMP and nitric oxide generators

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The efficacy of nicotinic transmission in the rat superior cervical ganglion in vitro (24–26°C) was estimated by extracellular recording of the postganglionic compound action potential response to stimulation of the preganglionic nerve at a slow rate (one shock every 60 s). Atropine (2 μM) was included to block muscarinic transmission, and hexamethonium (200–250 μM) was used to produce a submaximal response sensitive to potentiation and inhibition of nicotinic transmission. Upon exposure to 1–100 μM 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-Br-cGMP), nicotinic transmission was potentiated by6 ± 1% (n = 4) to89 ± 5% (n = 5) in a dose-dependent manner. 8-Bromo-adenosine 3′,5′-cyclic monophosphate (8-Br-cAMP, 10–100 μM) also potentiated nicotinic transmission (3.8 ± 0.3% (n = 3) to43 ± 4% (n = 3)). H However, 8-Br-cGMP was at least 2-fold more effective than 8-Br-cAMP. Sodium nitroprusside (0.1 μM to 1 mM) and sodium azide (0.1–100 μM) were used to stimulate the formation of endogenous cGMP 52. Nicotinic transmission was potentiated by these substances also. The response was increased by3.4 ± 0.7% (n = 4) to32 ± 2% (n = 5) upon exposure to 0.1–100 μM sodium nitroprusside, and by5.5 ± 0.9% (n = 3) to18 ± 4% (n = 4) upon exposure to 0.1–100 μM sodium azide. Ferricyanide ion (10–100 μM) appeared to be ineffective, as would be expected if the effect of nitroprusside was due to the nitric oxide rather than the cyanide or ferric moieties. A small increase in the response was observed when the extracellular concentration of K + was increased by about 300 μM (100 μM potassium ferricyanide or 300 μM KCl). These data are consistent with the hypothesis that cGMP may mediate a potentiation of nicotinic synaptic transmission and/or increased neuronal excitability in the sympathetic ganglion, and that this system could be activated by local production of a substance similar to endothelium-derived relaxant factor.