Endogenous nitric oxide inhibits nanc but not cholinergic
neurotransmission to circular muscle of guinea pig ileum.
Yunker, Anne Marie R., and James J. Galligan.
Department of Pharmacology and Toxicology and Neuroscience Program,
Michigan State University, E. Lansing, MI 48824
APStracts 3:0131G, 1996.
Nitric oxide (NO) mediates neurogenic relaxations of gastrointestinal
(GI) smooth muscle. NO synthase (NOS) inhibitors also alter
neurogenic contractions, suggesting NO modulates excitatory
neurotransmitter release. In circular muscle-myenteric plexus
preparations, guanethidine and either scopolamine or CP-96,345, a
neurokinin-1 receptor (NK1r) antagonist, were used to isolate
nonadrenergic, noncholinergic (NANC) or cholinergic contractions,
respectively. NOS inhibitors and hemoglobin potentiated neurogenic
NANC but not cholinergic contractions and did not affect NK1r
agonist- (substance P methyl ester (SPME)) induced contractions.
Sodium nitroprusside (SNP), a NO donor, attenuated NANC and
cholinergic neurogenic contractions, but cholinergic contractions
were less sensitive to SNP. SNP partially attenuated SPME-induced
contractions, and apamin reduced inhibition of NANC contractions by
SNP. Bethanechol responses were not affected by SNP. These data
indicate NANC but not cholinergic contractions are inhibited by
endogenous NO, suggesting differential regulation of release of
tachykinins and acetylcholine from enteric nerves. NK1r- but not
muscarinic receptor-activated postjunctional pathways are also
inhibited by NO. Therefore, prejunctional and postjunctional
modulation of NANC contractions are mechanisms for inhibition of GI
motility by endogenous NO.
Received 9 February 1995; accepted in final form 19 June 1996.
APS Manuscript Number G57-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96