title: Nitric oxide induces muscular relaxation via cyclic GMP-dependent and -independent mechanisms in the longitudinal muscle of the mouse duodenum.
abstract: The aim of this study was to investigate, in mouse duodenum, the role of nitric oxide (NO) in the relaxation of longitudinal muscle evoked by nerve activation and the coupled action mechanism. Electrical field stimulation (EFS; 0.5 ms, 10-s train duration, supramaximal voltage, at various frequencies) under nonadrenergic noncholinergic conditions evoked muscular relaxation occasionally followed, at the higher stimulus frequencies, by rebound contractions. Inhibition of the synthesis of NO by N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) virtually abolished the evoked relaxation. The relaxation was reduced also by apamin (0.1 microM) and by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), a guanylyl cyclase inhibitor. The coadministration of apamin and ODQ produced additive effects on the responses to EFS. Sodium nitroprusside (0.1-100 microM) produced a concentration-dependent reduction of the phasic spontaneous activity and at the highest dose used suppressed phasic activity and induced muscular relaxation. These effects were tetrodotoxin and L-NAME resistant and were antagonized both by apamin and by ODQ. 8-Bromoguanosine 3',5'-cyclic monophosphate (0.1-100 microM) reduced in a concentration-dependent manner the spontaneous mechanical activity and at 100 microM suppressed the phasic activity and induced muscular relaxation, not antagonized by apamin. This study indicates that NO is the primary transmitter released by inhibitory nerves supplying the longitudinal muscle of mouse duodenum and that guanylate cyclase stimulation and opening of Ca(2+)-dependent K(+) channels are independent mechanisms working in parallel to mediate NO action.
authors.affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia Generale, Università di Palermo, 90128 Palermo, Italy. rserio@unipa.it
authors.forename: Rosa
authors.initials: R
authors.lastname: Serio
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Zizzo
authors.forename: Flavia
authors.initials: F
authors.lastname: Mulè
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D009599:Nitroprusside; D009569:Nitric Oxide; D006152:Cyclic GMP