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Modulation by nitric oxide of spontaneous motility of the rat isolated duodenum: role of tachykinins
Author(s) -
MartinezCuesta M.A.,
Esplugues J.V.,
Whittle B.J.R.
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.tb15542.x
Subject(s) - endocrinology , hexamethonium , guanethidine , medicine , tetrodotoxin , phentolamine , nitroarginine , motility , nitric oxide synthase , omega n methylarginine , biology , chemistry , nitric oxide , acetylcholine , stimulation , genetics
1 Incubation of proximal segments of the rat isolated duodenum with N G ‐nitro‐L‐arginine (L‐NOARG; 3–100 μ m ) produced a concentration‐dependent increase in both resting tone and the amplitude of the spontaneous contractions. These effects were attenuated by concurrent incubation with L‐arginine (1 mM) but not D‐arginine (1 mM). 2 These changes in resting tone and motility induced by L‐NOARG (30 μ m ) were substantially reduced by concurrent incubation with tetrodotoxin (1 μ m ) or hexamethonium (10 μ m ), implicating the involvement of a local neuronal response. 3 The L‐NOARG‐induced increase in duodenal motility was not, however, inhibited by atropine (1 μ m ), guanethidine (6.4 μ m ) phentolamine (1 μ m ), or indomethacin (10 μ m ), indicating a non‐cholinergic, non‐adrenergic and non‐prostanoid‐mediated contractile response. 4 The NK 1 /NK 2 tachykinin receptor antagonist, (D‐Pro 2 , D‐Trp 7,9 substance P, 1–10 μ m ), and the NK 2 ‐receptor antagonists, MEN 10,207 and MEN 10,376 (1–5 μ m ), concentration‐dependently reduced the effect of L‐NOARG (30 μ m ) on spontaneous duodenal motility. 5 The resting tone and amplitude of the spontaneous contractions was likewise increased by incubation with N G ‐monomethyl‐L‐arginine (L‐NMMA; 100–1000 μ m ). However, incubation with L‐NMMA (100 μ m ) attenuated the actions of more potent L‐NOARG (30 μ m ) on resting motility. 6 Administration of E.coli endotoxin (3 mg kg −1 , i.v.) to the rat 5 h prior to tissue removal, at a time of known induction of NO synthase, reduced the amplitude of spontaneous contractions of the isolated duodenum, an effect inhibited by pretreatment of the rats with dexamethasone (1 mg kg −1 ) 2 h prior to endotoxin challenge. 7 These findings indicate a role of endogenous NO in the modulation of spontaneous tone and motility in the rat duodenum. Induction of NO synthase may result in a reduction in spontaneous motility of the tissue. By contrast, inhibition of constitutive NO biosynthesis unmasks a contractile response that is neuronally mediated and involves tachykinin NK 2 receptors.