title: Muscarinic receptor activation is a prerequisite for the endogenous release of nitric oxide modulating nicotinic transmission within the coeliac ganglion in the rabbit.
abstract: The aim of the present study was to investigate whether the activation of muscarinic receptors is a preliminary step to the endogenous release of nitric oxide modulating nicotinic transmission within the prevertebral ganglia. This work has been performed 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 supramaximal intensity was applied to the splanchnic nerves, gradual depression of fast nicotinic transmission occurred: the pulses do not systematically elicit action potentials, but very often elicit excitatory postsynaptic potentials only. The use of pharmacological agents that interfere with the nitric oxide pathway such as L-arginine (precursor of nitric oxide) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger) demonstrated that nitric oxide modulates this depression phenomenon by facilitating or inhibiting the nicotinic transmission of the ganglionic neurons. A nitric oxide donor (diethylamine/nitric oxide complex) induced an inhibition of the nicotinic synaptic transmission. In the presence of the muscarinic receptors antagonist atropine, L-arginine and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide failed to modify the nicotinic transmission of the ganglionic neurons but diethylamine/nitric oxide complex was still able to inhibit it. These results demonstrate that in the coeliac ganglion, the activation of muscarinic cholinergic receptors is a prerequisite for the activation of neuronal nitric oxide synthase in preganglionic fibres. The nitric oxide released then exerts a facilitation or an inhibition of the nicotinic transmission of the ganglionic neurons. Atropine triggered a facilitation of the nicotinic transmission when superfused alone and an inhibition when superfused in the presence of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. These results confirm that muscarinic receptors activate the nitric oxide pathway modulating the nicotinic transmission of the prevertebral neurons. Our results also demonstrate that when the nitric oxide pathway is blocked, activation of muscarinic receptors leads to facilitation of the nicotinic transmission. Our study brings new insights concerning the modulation by nitric oxide and by muscarinic receptors of the synaptic transmission within the prevertebral ganglia.
authors.affiliation: Département de Physiologie et Neurophysiologie ESA-CNRS 6034, Faculté des Sciences et Techniques de St Jérôme, Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Quinson
authors.forename: J P
authors.initials: JP
authors.lastname: Miolan
authors.forename: J P
authors.initials: JP
authors.lastname: Niel
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D009589:Nitrogen Oxides; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D001565:Benzoates; D006834:Hydrazines; D007093:Imidazoles; D018727:Muscarinic Antagonists; D009589:Nitrogen Oxides; D011976:Receptors, Muscarinic; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D009538:Nicotine; D001285:Atropine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine