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The nitric oxide‐cyclic GMP pathway and synaptic plasticity in the rat superior cervical ganglion
Author(s) -
Southam Eric,
Charles Sarah L.,
Garthwaite John
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15703.x
Subject(s) - soluble guanylyl cyclase , neurotransmission , long term potentiation , chemistry , superior cervical ganglion , excitatory postsynaptic potential , nitric oxide , synaptic plasticity , forskolin , stimulation , endocrinology , medicine , biology , biochemistry , receptor , cyclic gmp
1 We have investigated the possibility that nitric oxide (NO) and soluble guanylyl cyclase, an enzyme that synthesizes guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) in response to NO, contributes to plasticity of synaptic transmission in the rat isolated superior cervical ganglion (SCG). 2 Exposure of ganglia to the NO donor, nitroprusside, caused a concentration‐dependent accumulation of cyclic GMP which was augmented in the presence of the phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine. The compound, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), a selective inhibitor of soluble guanylyl cyclase, completely blocked this cyclic GMP response. 3 As assessed by extracellular recording, nitroprusside (100 μ m ) and another NO donor, S‐nitrosoglutathione (30 μ m ) increased the efficacy of ganglionic synaptic transmission in response to electrical stimulation of the preganglionic nerve, an effect that was reversible and which could be replicated by the cyclic GMP analogue, 8‐bromo‐cyclic GMP. Ganglionic depolarizations resulting from stimulation of nicotinic receptors with carbachol were not increased by nitroprusside. The potentiating actions of the NO donors on synaptic transmission, but not that of 8‐bromo‐cyclic GMP, were inhibited by ODQ. 4 Brief tetanic stimulation of the preganglionic nerve resulted in a long‐term potentiation (LTP) of synaptic transmission that was unaffected by ODQ, either in the absence or presence of the NO synthase inhibitor, N G ‐nitro‐L‐arginine (L‐NOARG, 100 μ m ). A lack of influence of L‐NOARG was confirmed in intracellular recordings of LTP of the excitatory postsynaptic potential. Furthermore, under conditions where tetanically‐induced LTP was saturated, nitroprusside was still able to potentiate synaptic transmission, as judged from extracellular recording. 5 We conclude that NO is capable of potentiating ganglionic neurotransmission and this effect is mediated through the stimulation of soluble guanylyl cyclase and the accumulation of cyclic GMP. However, this potentiation is distinct from LTP of nicotinic synaptic transmission, in which neither NO nor soluble guanylyl cyclase appear to participate.