Modulation by nitric oxide of spontaneous motility of the rat isolated duodenum: Role of tachykinins

1 Incubation of proximal segments of the rat isolated duodenum with NG-nitro-L-arginine (L-NOARG; 3-100 mu 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...

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Detalles Bibliográficos
Autores: MARTINEZCUESTA, MA, Esplugues, JV, Whittle, BJR
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1996
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p10547
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/10547
Access Level:acceso abierto
Palabra clave:duodenal motility
nitric oxide synthase
NO
tachykinins
NK2 receptors
NANC contractile response
Descripción
Sumario:1 Incubation of proximal segments of the rat isolated duodenum with NG-nitro-L-arginine (L-NOARG; 3-100 mu 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 mu M) were substantially reduced by concurrent incubation with tetrodotoxin (1 mu M) or hexamethonium (10 mu 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 mu M), guanethidine (6.4 mu M) phentolamine (1 mu M), or indomethacin (10 mu M), indicating a noncholinergic, non-adrenergic and non-prostanoid-mediated contractile response. 4 The NK1/NK2 tachykinin receptor antagonist, (D-Pro(2), D-Trp(7,9) substance P, 1-10 mu M), and the NK2-receptor antagonists, MEN 10,207 and MEN 10,376 (1-5 mu M), concentration-dependently reduced the effect of L-NOARG (30 mu 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 mu M). However, incubation with L-NMMA (100 mu M) attenuated the actions of more potent L-NOARG (30 mu 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 renown 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 NK2 receptors.