Nitric oxide-sensitive guanylyl cyclase inhibits acetylcholine release and excitatory motor transmission in the guinea-pig ileum
This study examined the mechanism through which nitric oxide inhibits the release of acetylcholine and excitatory motor neurotransmission in the guinea-pig ileum. The selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), concentration-de...
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Published in | Neuroscience Vol. 82; no. 2; pp. 623 - 629 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Elsevier Ltd
01.10.1997
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Subjects | |
Online Access | Get full text |
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Summary: | This study examined the mechanism through which nitric oxide inhibits the release of acetylcholine and excitatory motor neurotransmission in the guinea-pig ileum. The selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1
H-[1,2,4]oxadiazolo[4,3-
a]quinoxalin-1-one (ODQ), concentration-dependently enhanced both basal release (−log EC
50: 6.8) and electrically (10
Hz) -evoked release (−log EC
50: 6.0) of [
3H]acetylcholine from longitudinal muscle-myenteric plexus preparations preincubated with [
3H]choline. The increase by ODQ of basal release appeared to be exocytotic since it was prevented by tetrodotoxin (300
nM) and absence of calcium from the superfusion medium. In addition, ODQ (1
μM) increased the electrically-evoked tachykininergic and cholinergic muscle contractions as measured in the presence of scopolamine (100
nM) or of the neurokinin-1 receptor antagonist CP 99994 (100
nM), respectively. The nitric oxide synthase inhibitor
l-
N
G-nitro-arginine (100
μM) behaved similar to ODQ and increased cholinergic and tachykininergic motor neurotransmission. The nitric oxide-independent activator of soluble guanylyl cyclase, 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole, concentration-dependently inhibited the electrically evoked acetylcholine release (−log EC
50: 6.0) and longitudinal muscle contractions (−log EC
50: 5.7). ODQ (10
μM) antagonized the effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole.
The results suggest that endogenous nitric oxide tonically activates soluble guanylyl cyclase in myenteric neurons which leads to inhibition of the release of the excitatory transmitters acetylcholine and substance P. ODQ prevents the effects of nitric oxide and thus facilitates cholinergic and tachykininergic motor neurotransmission in the guinea-pig ileum. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0306-4522 1873-7544 |
DOI: | 10.1016/S0306-4522(97)00308-4 |