Muscarinic receptor activation is a prerequisite for the endogenous release of nitric oxide modulating nicotinic transmission within the coeliac ganglion in the rabbit

The aim of the present study was to investigate whether the activation of m uscarinic receptors is a preliminary step to the endogenous release of nitr ic 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 intra cellular recording techniques. When a train of pulses of supramaximal inten sity was applied to the splanchnic nerves, gradual depression of fast nicot inic 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 path way such as L-arginine (precursor of nitric oxide) or 2-(4-carboxyphenyl)-4 ,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger) demon strated that nitric oxide modulates this depression phenomenon by facilitat ing or inhibiting the nicotinic transmission of the ganglionic neurons. A n itric 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-t etramethylimidazoline-1-oxyl-3-oxide failed to modify the nicotinic transmi ssion of the ganglionic neurons but diethylamine/nitric oxide complex was s till able to inhibit it. These results demonstrate that in the coeliac gang lion, the activation of muscarinic cholinergic receptors is a prerequisite for the activation of neuronal nitric oxide synthase in preganglionic fibre s. 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 in hibition when superfused in the presence of 2-(4-carboxyphenyl)-4,4,5,5-tet ramethylimidaziline-oxyl-3-oxide. These results confirm that muscarinic rec eptors activate the nitric oxide pathway modulating the nicotinic transmiss ion 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 prevertebr al ganglia. (C) 1999 IBRO. Published by Elsevier Science Ltd.