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Effect of Cu2+ on relaxations to the nitrergic neurotransmitter, NO and S-nitrosothiols in the rat gastric fundus. 1996

J G De Man, and B Y De Winter, and G E Boeckxstaens, and A G Herman, and P A Pelckmans
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.

1. The effects of addition of Cu2+ and chelation of Cu2+ were studied on relaxations in response to S-nitrosothiols and on relaxations to non-adrenergic non-cholinergic (NANC) nerve stimulation, nitric oxide (NO) and glyceryl trinitrate (GTN) in the rat gastric fundus. 2. The S-nitrosothiols S-nitroso-L-cysteine (NOCys, 1-300 nM), S-nitrosoglutathione (GSNO, 0.01-3 microM) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 0.01-3 microM) induced concentration-dependent relaxations of the rat gastric fundus muscle strip. The relaxant potencies of the S-nitrosothiols were NOCys > SNAP > GSNO. Relaxations to NOCys were transient and comparable to those to NANC nerve stimulation and NO whereas relaxations to GSNO and SNAP were sustained. The relaxations to NOCys, GSNO and SNAP were significantly and concentration-dependently enhanced by CuSO4 (3-30 microM). The order of relaxant potency in the presence of CuSO4 was reversed to GSNO approximately SNAP > NOCys. 3. In the presence but not in the absence of 0.1 microM GSNO, CuSO4 (1 microM) induced a rapid and transient relaxation which was inhibited by the superoxide radical generator, pyrogallol (30 microM). CuCl2 but not FeSO4 mimicked the effect of CuSO4. 4. Electrical stimulation (0.5-8 Hz) of the rat gastric fundus strips induced frequency-dependent relaxations which were previously shown to be nitrergic in nature and which were not affected by CuSO4 (3-30 microM). Relaxations to NO (3-100 nM) and GTN (0.01-1 microM) were not affected by 3 and 10 microM CuSO4 but were inhibited by 30 microM CuSO4. 5. The Cu2+ chelator, bathocuproine (3-30 microM) significantly and concentration-dependently inhibited the relaxations to NOCys (0.01-3 microM), GSNO (0.01-10 microM) and SNAP (0.01-3 microM). The inhibitory effect of 10 microM bathocuproine was reversed by 3 microM CuSO4. 6. Bathocuproine (3-30 microM) had no effect on the relaxations to NANC nerve stimulation (0.5-8 Hz) or on the concentration-response curve to NO (0.01-0.3 microM), whereas relaxations to GTN (0.01-1 microM) were significantly inhibited by 30 microM bathocuproine. 7. From these results we conclude that relaxations to S-nitrosothiols and to nitrergic stimulation of the rat gastric fundus are differentially affected by addition and chelation of Cu2+, suggesting that the nitrergic NANC neurotransmitter in the rat gastric fundus is not an S-nitrosothiol but is more likely to be free nitric oxide.

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
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
D009603 Nitroso Compounds Organic compounds containing the nitroso (-N Compounds, Nitroso
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
D005748 Gastric Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Fundus, Gastric
D005996 Nitroglycerin A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives. Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
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
D013438 Sulfhydryl Compounds Compounds containing the -SH radical. Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl

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