Nerve-induced release of nitric oxide exerts dual effects on nicotinic transmission within the coeliac ganglion in the rabbit

Abstract

The involvement of nitric oxide in the modulation of nicotinic activation was investigated in vitro in isolated rabbit coeliac ganglion. The electrical activity of the ganglionic neurons was recorded using intracellular recording techniques. When a train of pulses of supramaximum intensity was applied to the splanchnic nerves, gradual depression of fast nicotinic activation occurred: the pulses do not systematically elicit action potentials, but very often elicit excitatory postsynaptic potentials only. This phenomenon appeared between 15 and 20 Hz and increased with the frequency of stimulation. It was not related to any change in the membrane potential of the ganglionic neurons. For a given frequency, the depression appeared progressively and it was particularly strong at the end of the train. The use of pharmacological agents that interfere with the nitric oxide pathway, such as l-arginine (precursor of nitric oxide), d-arginine (non-precursor of nitric oxide), N ω -nitro- l-arginine and N ω -nitro- l-arginine methyl ester (inhibitors of nitric oxide synthase), and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger), demonstrated that nitric oxide modulated this depression phenomenon by exerting a dual effect on the nicotinic activation, i.e. facilitation or inhibition. Agents interfering with the guanosine 3′,5′-cyclic monophosphate pathway, such as oxadiazolo[4,3-a] quinoxalin-1-one (selective inhibitor of the nitric oxide-activated soluble guanylate cyclase) and zaprinast (selective inhibitor of the phosphodiesterases involved in the guanosine 3′,5′-cyclic monophosphate pathway) demonstrated that only the facilitatory effect of nitric oxide on the nicotinic activation was mediated through the guanosine 3′,5′-cyclic monophosphate pathway. The mechanism sustaining the inhibitory effect remains to be determined. By modulating the nicotinic activation, nitric oxide plays a role in the integrative properties of the prevertebral ganglia. This opens new perspectives with regard to the control of visceral functions by the prevertebral level of regulation.