title: Nitric oxide contracts longitudinal smooth muscle of opossum oesophagus via excitation-contraction coupling.
abstract: 1. The effects of sodium nitroprusside (SNP) and diethylenetriamine/nitric oxide adduct (DETA/NO), putative nitric oxide (NO) donors, on opossum oesophageal longitudinal smooth muscle were investigated using isometric tension and intracellular micro-electrode recordings. 2. SNP produced concentration-dependent contractions of oesophageal longitudinal smooth muscle with an EC(50) of 239.6 +/- 78.2 microM (mean +/- S.E.M., n = 10). Maximal contraction induced by SNP (1 mM) was about 75.5 +/- 8.5 % (n = 10) of the 60 mM KCl-induced contraction. The SNP-induced contraction was resistant to tetrodotoxin (TTX; 1 microM), but abolished by nifedipine (1 microM), as well as by niflumic acid (300 microM) and 9-anthroic acid (9-AC; 1 mM), Ca(2+)-activated Cl(-) channel blockers. 3. DETA/NO at concentrations of 100 and 500 microM induced 83.1 +/- 24.4 and 104.1 +/- 34.9 % of the 60 mM KCl-induced contraction (n = 4), respectively, which was abolished by nifedipine (1 microM), niflumic acid (300 microM) and 9-AC (1 mM). 4. Pre-application of 1H-[1,2,4]oxidiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) (10 microM), a guanylate cyclase inhibitor, significantly inhibited the SNP-induced contraction, whereas 8-bromo-cGMP (1 mM), a membrane-permeable analogue of cGMP, mimicked the SNP-induced contraction. 5. Intracellular recordings revealed that SNP (300 microM) depolarized resting membrane potentials (RMPs) and increased the frequency of spontaneous spike-like action potentials. However, these electrical alterations were eliminated by pretreatment with niflumic acid (300 microM). 6. These results suggest that NO produces an excitation-contraction coupling in opossum oesophageal longitudinal smooth muscle via a cGMP-dependent signalling pathway. This contraction depends on extracellular Ca(2+) entry through activation of L-type Ca(2+) channels.
authors.affiliation: Gastrointestinal Disease Research Unit and Departments of Medicine and Physiology, Queen's University, Kingston, Ontario, Canada K7L 5G2.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W G
authors.initials: WG
authors.lastname: Paterson
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009893:Opossums; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D014226:Triazenes; D009599:Nitroprusside; D009569:Nitric Oxide; D013779:Tetrodotoxin; D006152:Cyclic GMP; D009543:Nifedipine