Biomaterial Database

Inhibition of relaxations to nitrergic stimulation of the mouse anococcygeus by duroquinone. 1995

E Lilley, and A Gibson

Biomedical Sciences Division, King's College London.

1. The role of copper/zinc superoxide dismutase (Cu/Zn SOD) in protection of nitrergic neurotransmission in the mouse anococcygeus was investigated by use of duroquinone (DQ), which generates superoxide anions within tissues via reduction by flavoprotein enzymes. 2. In control anococcygeus muscles, DQ (10-100 microM) produced concentration-related inhibition (-log IC40 = 4.41) of relaxations to exogenous nitric oxide (NO; 15 microM). Nitrergic relaxations induced by field stimulation (10 Hz; 10 s train) were much less affected, 100 microM DQ reducing nitrergic relaxations by only 14 +/- 6%. 3. Following incubation with the Cu/Zn SOD inhibitor, diethyldithiocarbamate (DETCA; 3 mM; 45 min incubation; 10 min washout), the inhibitory effects of DQ on relaxations to NO were potentiated (-log IC40 = 5.22), and clear, concentration-related inhibitions of nitrergic relaxations were now observed (-log IC40 = 4.54). In both cases, these inhibitions were partially reversed by Cu/Zn SOD (250 u ml-1). In DETCA-treated tissues, DQ (100 microM) also reduced relaxations to sodium nitroprusside (1 microM) and S-nitroso-glutathione (30 microM), but potentiated those to 8-Br-cyclic GMP (100 microM). 4. Neither hydroquinone (HQ: 100 microM) nor 1,4-benzoquinone (BQ: 100 microM), both of which reduced responses to exogenous NO, inhibited relaxations induced by field stimulation in DETCA-treated tissues. Indeed, when added during DQ-induced inhibition of nitrergic relaxations, both HQ and BQ produced partial reversal of the block. 5. DQ had no effect on the detection of superoxide anions estimated via the xanthine:xanthine oxidase chemiluminescence assay, or of authentic NO as measured by a chemical microsensor. However, the detection of both superoxide anions and NO in these assays was inhibited by inclusion of either HQ or BQ. 6. The results support the proposal that nitrergic transmission in the peripheral nervous system is protected by Cu/Zn SOD activity in the region of the neuroeffector junction, and this may explain the lack of effect of superoxide anion generating drugs such as DQ. Such an explanation does not hold for either HQ or BQ, which appear to be acting directly as free radical scavengers in these experiments.

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
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
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002614	Chelating Agents	Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.	Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D004050	Ditiocarb	A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.	Diethyldithiocarbamate,Diethylcarbamodithioic Acid,Diethyldithiocarbamic Acid,Dithiocarb,Ditiocarb Sodium,Ditiocarb, Ammonium Salt,Ditiocarb, Bismuth Salt,Ditiocarb, Lead Salt,Ditiocarb, Potassium Salt,Ditiocarb, Sodium Salt,Ditiocarb, Sodium Salt, Trihydrate,Ditiocarb, Tin(4+) Salt,Ditiocarb, Zinc Salt,Imuthiol,Sodium Diethyldithiocarbamate,Thiocarb,Zinc Diethyldithiocarbamate,Ammonium Salt Ditiocarb,Bismuth Salt Ditiocarb,Diethyldithiocarbamate, Sodium,Diethyldithiocarbamate, Zinc,Lead Salt Ditiocarb,Potassium Salt Ditiocarb,Sodium Salt Ditiocarb,Sodium, Ditiocarb,Zinc Salt Ditiocarb
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006873	Hydroquinones	Derivatives of hydroquinone (1,4-dihydrobenzene) made by reduction of BENZOQUINONES.	Quinol,p-Dihydroxybenzenes,para-Dihydroxybenzenes,Quinols,p Dihydroxybenzenes,para Dihydroxybenzenes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia