Inhibition of nitrergic relaxations by a selective inhibitor of the soluble guanylate cyclase. 1996

S Cellek, and L Kasakov, and S Moncada
Wellcome Research Laboratories, Beckenham, Kent.

1. The actions of 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), a specific inhibitor of the soluble guanylate cyclase (SGC), were investigated in the rabbit anococcygeus muscle. 2. ODQ (1 nM-1 microM) inhibited in a concentration-dependent manner the relaxations induced by electrical field stimulation (EFS; 50 V, 0.3 ms duration, 1 Hz, for 5 s, every 120 s). 3. ODQ (1 microM) also inhibited the relaxations elicited by EFS (50 V, 0.3 ms duration, 1, 2.5, 5, 10 Hz, for 5 s) and sodium nitroprusside (SNP; 1 microM) without affecting those induced by isoprenaline (1 microM), atrial natriuretic peptide (ANP; 100 nM) or an analogue of cyclic GMP (8-pCPT-cyclic GMP; 500 microM). 4. ODQ (1 microM) inhibited the elevations in the concentration of cyclic GMP induced by SNP or EFS, but not by ANP. ODQ did not affect the concentrations of cyclic AMP. 5. Nitrergic relaxation in this tissue appears, therefore, to be mediated via activation of SGC.

UI MeSH Term Description Entries
D008297 Male Males
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010069 Oxadiazoles Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms. Oxadiazole
D011810 Quinoxalines Quinoxaline
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme

Related Publications

S Cellek, and L Kasakov, and S Moncada
September 2000, Biochemistry,
S Cellek, and L Kasakov, and S Moncada
January 1982, Acta biologica et medica Germanica,
S Cellek, and L Kasakov, and S Moncada
September 2008, Surgery,
S Cellek, and L Kasakov, and S Moncada
January 1980, Journal of cyclic nucleotide research,
S Cellek, and L Kasakov, and S Moncada
January 1998, Acta physiologica Scandinavica,
S Cellek, and L Kasakov, and S Moncada
September 2015, Bioorganic & medicinal chemistry,
S Cellek, and L Kasakov, and S Moncada
November 1994, Biokhimiia (Moscow, Russia),
S Cellek, and L Kasakov, and S Moncada
December 2006, Current opinion in structural biology,
S Cellek, and L Kasakov, and S Moncada
January 2011, Biomeditsinskaia khimiia,
Copied contents to your clipboard!