Online citations, reference lists, and bibliographies.
← Back to Search

Differential Sensitivity Of Guanylyl Cyclase And Mitochondrial Respiration To Nitric Oxide Measured Using Clamped Concentrations*

T. Bellamy, C. Griffiths, J. Garthwaite
Published 2002 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Nitric oxide (NO) signal transduction may involve at least two targets: the guanylyl cyclase-coupled NO receptor (NOGCR), which catalyzes cGMP formation, and cytochrome c oxidase, which is responsible for mitochondrial O2 consumption and which is inhibited by NO in competition with O2. Current evidence indicates that the two targets may be similarly sensitive to NO, but quantitative comparison has been difficult because of an inability to administer NO in known, constant concentrations. We addressed this deficiency and found that purified NOGCR was about 100-fold more sensitive to NO than reported previously, 50% of maximal activity requiring only 4 nm NO. Conversely, at physiological O2concentrations (20–30 μm), mitochondrial respiration was 2–10-fold less sensitive to NO than estimated beforehand. The two concentration-response curves showed minimal overlap. Accordingly, an NO concentration maximally active on the NOGCR (20 nm) inhibited respiration only when the O2concentration was pathologically low (50% inhibition at 5 μm O2). Studies on brain slices under conditions of maximal stimulation of endogenous NO synthesis suggested that the local NO concentration did not rise above 4 nm. It is concluded that under physiological conditions, at least in brain, NO is constrained to target the NOGCR without inhibiting mitochondrial respiration.
This paper references
10.1038/336385A0
Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain
J. Garthwaite (1988)
10.1111/j.1460-9568.1990.tb00396.x
Immunocytochemistry of cGMP in the Cerebellum of the Immature, Adult, and Aged Rat: the Involvement of Nitric Oxide. A Micropharmacological Study
J. Vente (1990)
10.1111/J.1471-4159.1991.TB03468.X
Excitatory Amino Acid Receptors Coupled to the Nitric Oxide/Cyclic GMP Pathway in Rat Cerebellum During Development
E. Southam (1991)
Pharmacology of the second messenger, cyclic guanosine 3',5'-monophosphate, in the cerebellum.
P. Wood (1991)
10.1016/S0005-2728(99)00016-X
Mammalian nitric oxide synthases.
D. Stuehr (1992)
10.1016/0028-3908(94)90022-1
Models of the diffusional spread of nitric oxide: Implications for neural nitric oxide signalling and its pharmacological properties
J. Wood (1994)
10.1016/0014-5793(94)01290-3
Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase
G. Brown (1994)
10.1146/ANNUREV.PH.57.030195.003343
Nitric oxide signaling in the central nervous system.
J. Garthwaite (1995)
Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase.
A. Schrammel (1996)
10.1021/BI9519718
Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide.
J. R. Stone (1996)
10.1006/BBRC.1997.7470
Dissociation of nitric oxide from soluble guanylate cyclase.
V. Kharitonov (1997)
10.1016/S0014-5793(97)01258-1
Kinetics of the inhibition of mitochondrial respiration by NO
A. Koivisto (1997)
10.1038/SJ.BMT.1701381
Blood Stem Cell Transplantation
S. Kelsey (1998)
10.1021/BI9814989
Regeneration of the ferrous heme of soluble guanylate cyclase from the nitric oxide complex: acceleration by thiols and oxyhemoglobin.
P. E. Brandish (1998)
10.1042/BJ3350125
Functional properties of a naturally occurring isoform of soluble guanylyl cyclase.
M. Russwurm (1998)
10.1074/jbc.273.30.18709
Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes*
X. Liu (1998)
10.1073/PNAS.96.26.14753
A molecular basis for nitric oxide sensing by soluble guanylate cyclase.
Y. Zhao (1999)
10.1021/BI990154V
Regulation of nitric oxide-responsive recombinant soluble guanylyl cyclase by calcium.
S. J. Parkinson (1999)
10.1007/BFB0033669
Soluble guanylyl cyclase: structure and regulation.
D. Koesling (1999)
10.1006/NIOX.1999.0253
A nitric oxide concentration clamp.
V. Zhelyaskov (1999)
10.1146/ANNUREV.PHARMTOX.39.1.191
Inhibition of nitric oxide synthase as a potential therapeutic target.
A. Hobbs (1999)
10.1073/PNAS.97.6.2928
Rapid desensitization of the nitric oxide receptor, soluble guanylyl cyclase, underlies diversity of cellular cGMP responses.
T. C. Bellamy (2000)
10.1016/S0005-2728(00)00238-3
Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase.
G. Brown (2001)
10.1074/JBC.M108666200
Differences in Three Kinetic Parameters Underpin the Unique Catalytic Profiles of Nitric-oxide Synthases I, II, and III*
J. Santolini (2001)
10.1111/j.1469-7793.2001.00855.x
The shaping of nitric oxide signals by a cellular sink
C. Griffiths (2001)
10.1074/JBC.M006677200
Sub-second Kinetics of the Nitric Oxide Receptor, Soluble Guanylyl Cyclase, in Intact Cerebellar Cells*
T. C. Bellamy (2001)
10.1074/JBC.M105587200
Guanylyl Cyclase/PSD-95 Interaction
M. Russwurm (2001)
10.1016/S0034-5687(01)00306-1
Tissue oxygen tension and brain sensitivity to hypoxia.
M. Erecińska (2001)
10.1021/BI002885X
In vitro activation of soluble guanylyl cyclase and nitric oxide release: a comparison of NO donors and NO mimetics.
J. D. Artz (2001)
10.1073/pnas.012368499
On the activation of soluble guanylyl cyclase by nitric oxide
T. C. Bellamy (2001)
10.1074/JBC.M110570200
Inhibition of Deactivation of NO-sensitive Guanylyl Cyclase Accounts for the Sensitizing Effect of YC-1*
M. Russwurm (2002)
10.1038/ncb775
Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide
U. Zabel (2002)
10.1038/nrm762
Does nitric oxide modulate mitochondrial energy generation and apoptosis?
S. Moncada (2002)
10.1046/j.1460-9568.2002.01930.x
Dynamics of nitric oxide during simulated ischaemia‐reperfusion in rat striatal slices measured using an intrinsic biosensor, soluble guanylyl cyclase
C. Griffiths (2002)
10.1016/S0968-0004(01)02035-7
Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector?
C. Cooper (2002)



This paper is referenced by
10.1111/apha.13443
Nitric oxide: To be or not to be an endocrine hormone?
Z. Bahadoran (2020)
10.1371/journal.pcbi.1008069
Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics
W. D. Haselden (2020)
10.5445/IR/1000096467
Stickstoffmonoxid - ein Faktor zur gezielten Steuerung hämatopoetischer Stammzellen? Auswirkungen auf das Proliferations- und Differenzierungsverhalten CD34$^{+}$ Zellen in vitro
J. Hümmer (2019)
10.3389/fneur.2019.01425
Targeted Metabolomic Profiling Reveals Association Between Altered Amino Acids and Poor Functional Recovery After Stroke
X. Wang (2019)
Early studies identifying the important roles of NO , cGMP and PKG in controlling blood pressure and blood flow and mediating penile erection
R. Fiscus (2018)
Targeting the NMDA receptor/NO signalling pathway following L-α aminoadipic acid-induced astrocytic impairment and associated changes in the structural plasticity of neurons
J. David (2018)
10.1016/j.niox.2018.04.011
Physiological activation and deactivation of soluble guanylate cyclase.
Benjamin G Horst (2018)
10.1074/jbc.M117.777243
Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism
A. San Martín (2017)
10.1039/c6sc00188b
From curiosity to applications. A personal perspective on inorganic photochemistry
P. C. Ford (2016)
10.1113/JP270297
From synaptically localized to volume transmission by nitric oxide
J. Garthwaite (2016)
10.33549/PHYSIOLRES.932833
The VO(2)-on kinetics in constant load exercise sub-anaerobic threshold reflects endothelial function and dysfunction in muscle microcirculation.
D. Maione (2015)
10.15407/UBJ87.06.064
THE EFFECT OF NITRIC OXIDE ON SYNAPTIC VESICLE PROTON GRADIENT AND MITOCHONDRIAL POTENTIAL OF BRAIN NERVE TERMINALS.
Tarasenko As (2015)
10.15407/ubj87.06.064
THE EFFECT OF NITRIC OXIDE ON SYNAPTIC VESICLE PROTON GRADIENT AND MITOCHONDRIAL POTENTIAL OF BRAIN NERVE TERMINALS.
A. Tarasenko (2015)
10.1161/JAHA.114.001474
Traumatic Brain Injury Disrupts Cerebrovascular Tone Through Endothelial Inducible Nitric Oxide Synthase Expression and Nitric Oxide Gain of Function
N. Villalba (2014)
10.1016/j.neuroscience.2014.08.021
Retrograde response in axotomized motoneurons: Nitric oxide as a key player in triggering reversion toward a dedifferentiated phenotype
D. González-Forero (2014)
10.1016/j.niox.2013.02.001
Photochemical delivery of nitric oxide.
P. C. Ford (2013)
10.1007/430_2013_102
Coordination Chemistry of Nitrosyls and Its Biochemical Implications
H. Lewandowska (2013)
10.1201/B15546-17
New Perspectives in Chemoresistant Ovarian Cancer
A. Y. Ali (2013)
Multiphotonic study of a new NADPH-derivative compound targeting NO-synthase
H. Wang (2013)
10.1007/978-1-62703-459-3_8
Real-time monitoring the spatiotemporal dynamics of intracellular cGMP in vascular smooth muscle cells.
Kara F. Held (2013)
10.1007/978-1-62703-459-3
Guanylate Cyclase and Cyclic GMP
T. Krieg (2013)
10.1021/ja408516w
Nitric oxide releasing materials triggered by near-infrared excitation through tissue filters.
Peter T. Burks (2013)
10.1016/j.resp.2012.03.016
Gas biology: Tiny molecules controlling metabolic systems
M. Kajimura (2012)
Nitric oxide signalling in hippocampal synaptic plasticity
B. Pigott (2012)
10.5772/28437
Nitric Oxide/Protein Kinase G-Iα Promotes c-Src Activation, Proliferation and Chemoresistance in Ovarian Cancer
R. Fiscus (2012)
10.1155/2012/391914
Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration
Ricardo M. Santos (2012)
10.1021/MP300139Y
Liposome encapsulation of a photochemical NO precursor for controlled nitric oxide release and simultaneous fluorescence imaging.
A. Ostrowski (2012)
10.3389/fphar.2012.00130
Sub-Nanomolar Sensitivity of Nitric Oxide Mediated Regulation of cGMP and Vasomotor Reactivity in Vascular Smooth Muscle
Kara F. Held (2012)
10.1074/jbc.M112.436022
Endothelial Nitric-oxide Synthase Activation Generates an Inducible Nitric-oxide Synthase-like Output of Nitric Oxide in Inflamed Endothelium*
J. L. Lowry (2012)
10.1007/978-1-61779-824-5_18
Protein kinase G (PKG): Involvement in Promoting Neural Cell Survival, Proliferation, Synaptogenesis, and Synaptic Plasticity and the Use of New Ultrasensitive Capillary-Electrophoresis-Based Methodologies for Measuring PKG Expression and Molecular Actions
R. Fiscus (2012)
10.1160/TH11-05-0319
Differentiation of cGMP-dependent and -independent nitric oxide effects on platelet apoptosis and reactive oxygen species production using platelets lacking soluble guanylyl cyclase.
N. Rukoyatkina (2011)
10.1016/j.mvr.2011.02.002
Temporal variations of the cell-free layer width may enhance NO bioavailability in small arterioles: Effects of erythrocyte aggregation.
P. Ong (2011)
See more
Semantic Scholar Logo Some data provided by SemanticScholar