scholarly journals Opposing actions of nitric oxide on synaptic inputs of identified interneurones in the central nervous system of the crayfish

2001 ◽  
Vol 204 (7) ◽  
pp. 1319-1332 ◽  
Author(s):  
H. Aonuma ◽  
P.L. Newland
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Sensory Nerve ◽  
Signal Transduction Pathway ◽  
Response Class ◽  
No Donor ◽  
Synaptic Inputs ◽  
Class 1 ◽  
Local Circuits

Little is known of the action of nitric oxide (NO) at the synaptic level on identified interneurones in local circuits that process mechanosensory signals. Here, we examine the action of NO in the terminal abdominal ganglion of the crayfish Pacifastacus leniusculus, where it has modulatory effects on the synaptic inputs of 17 identified ascending interneurones mediated by electrical stimulation of a sensory nerve. To analyse the role of NO in the processing of sensory signals, we bath-applied the NO donor SNAP, the NO scavenger PTIO, the nitric oxide synthase (NOS) inhibitor l-NAME, the NOS substrate l-arginine, a cyclic GMP (cGMP) analogue, 8-Br-cGMP, and the soluble guanylate cyclase (sGC) inhibitor ODQ. The effects of these chemicals on the synaptic inputs of the interneurones could be divided into two distinct classes. The NO donor SNAP enhanced the inputs to one class of interneurone (class 1) and depressed those to another (class 2). Neither the inactive isomer NAP nor degassed SNAP had any effect on the inputs to these same classes of interneurone. The NO scavenger PTIO caused the opposite effects to those of the NO donor SNAP, indicating that endogenous NO may have an action in local circuits. Preventing the synthesis of NO using l-NAME had the opposite effect to that of SNAP on each response class of interneurone. Increasing the synthesis of endogenous NO by applying l-arginine led to effects on both response classes of interneurone similar to those of SNAP. Taken together, these results suggested that NO was the active component in mediating the changes in amplitude of the excitatory postsynaptic potentials. Finally, the effects of 8-Br-cGMP were similar to those of the NO donor, indicating the possible involvement of a NO-sensitive guanylate cyclase. This was confirmed by preventing the synthesis of cGMP by sGC using ODQ, which caused the opposite effects to those of 8-Br-cGMP on the two response classes of interneurone. The results indicate that a NO-cGMP signal transduction pathway, in which NO regulates transmitter release from mechanosensory afferents onto intersegmental ascending interneurones, is probably present in the local circuits of the crayfish.

Nitric oxide decreases endothelin-1 secretion through the activation of soluble guanylate cyclase

2004 ◽  
Vol 286 (5) ◽  
pp. L984-L991 ◽  
Author(s):  
Lisa K. Kelly ◽  
Stephen Wedgwood ◽  
Robin H. Steinhorn ◽  
Stephen M. Black
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Primary Cultures ◽  
No Donor ◽  
Endothelin 1 ◽  
Cgmp Analog ◽  
Pulmonary Arterial ◽  
Long Acting ◽  
Arterial Endothelial Cells

The use of exogenous nitric oxide (NO) has been shown to alter the regulation of other endothelially derived mediators of vascular tone, such as endothelin-1 (ET-1). However, the interaction between NO and ET-1 appears to be complex and remains incompletely understood. One of the major actions of NO is the activation of soluble guanylate cyclase (sGC) with the subsequent generation of cGMP. Therefore, we undertook this study to test the hypothesis that NO regulates ET-1 production via the activation of the sGC/cGMP pathway. The results obtained indicated that the exposure of primary cultures of 4-wk-old ovine pulmonary arterial endothelial cells (4-wk PAECs) to the long-acting NO donor DETA NONOate induced both a dose- and time-dependent decrease in secreted ET-1. This decrease in ET-1 secretion occurred in the absence of changes in endothelin-converting enzyme-1 or sGC expression but in conjunction with a decrease in prepro-ET-1 mRNA. The changes in ET-1 release were inversely proportional to the cellular cGMP content. Furthermore, the NO-independent activator of sGC, YC-1, or treatment with a cGMP analog also produced significant decreases in ET-1 secretion. Conversely, pretreatment with the sGC inhibitor ODQ blocked the NO-induced decrease in ET-1. Therefore, we conclude that exposure of 4-wk PAECs to exogenous NO decreases secreted ET-1 resulting from the activation of sGC and increased cGMP generation.

scholarly journals Effects of nitroglycerin/L-cysteine on soluble guanylate cyclase: evidence for an activation/inactivation equilibrium controlled by nitric oxide binding and haem oxidation

2005 ◽  
Vol 390 (2) ◽  
pp. 625-631 ◽  
Author(s):  
Antonius C. F. Gorren ◽  
Michael Russwurm ◽  
Alexander Kollau ◽  
Doris Koesling ◽  
Kurt Schmidt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Soret Band ◽  
Flavin Mononucleotide ◽  
Independent Manner ◽  
No Donor ◽  
No Release ◽  
Glycerol Trinitrate ◽  
Haem Protein

GTN (nitroglycerin; glycerol trinitrate) causes dilation of blood vessels via activation of nitric oxide (NO)-sensitive sGC (soluble guanylate cyclase), a heterodimeric haem protein that catalyses the conversion of GTP into cGMP. Activation of sGC by GTN requires enzymatic or non-enzymatic bioactivation of the nitrate. Based on insufficient NO release and lack of spectroscopic evidence for formation of NO–sGC, the cysteine (Cys)-dependent activation of sGC by GTN was proposed to occur in an NO-independent manner. This extraordinary claim is questioned by the present findings. First, the effect of GTN/Cys was blocked by the NO scavenger oxyhaemoglobin, the superoxide-generating compound flavin mononucleotide and the haem-site sGC inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Secondly, at equi-effective concentrations, GTN/Cys and the NO donor 2,2-diethyl-1-nitroso-oxyhydrazine released identical amounts of NO. Finally, at sufficiently high rates of NO release, activation of sGC by GTN/Cys was accompanied by a shift of the Soret band from 431 to 399 nm, indicating formation of NO–sGC. In the absence of Cys, GTN caused haem oxidation, apparent as a shift of the Soret band to 392 nm, which was accompanied by inactivation of the NO-stimulated enzyme. These results suggest that the effect of GTN/Cys is the result of an activation/inactivation equilibrium that is controlled by the rate of NO release and haem oxidation.

The role of nitric oxide in the regulation of the electrical activity of the trigeminal nerve in the rat

2021 ◽  
Author(s):  
S.O. Svitko ◽  
K.S. Koroleva ◽  
G.F. Sitdikova ◽  
K.A. Petrova
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Trigeminal Nerve ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
The Body ◽  
No Donor ◽  
No Signaling

Nitric oxide (NO) is a gaseous signaling molecule that regulates a number of physiological functions, including its role in the formation of migraine has been established. NO is endogenously produced in the body from L-arginine by NO synthase. The NO donor, nitroglycerin, is a trigger of migraine in humans and is widely used in the modeling of this disease in animals, which suggests the involvement of components of the NO signaling cascade in the pathogenesis of migraine. Based on the results obtained, it was found that an increase in the concentration of both the substrate for the synthesis of NO, L-arginine, and the NO donor, sodium nitroprusside, has a pro-nociceptive effect in the afferents of the trigeminal nerve. In this case, the effect of sodium nitroprusside is associated with the activation of intracellular soluble guanylate cyclase. Key words: nitric oxide, migraine, trigeminal nerve, L-arginine, guanylate cyclase, sodium nitroprusside, nociception.

Inhibition of guanylate cyclase stimulation by NO and bovine arterial relaxation to peroxynitrite and H2O2

1999 ◽  
Vol 277 (3) ◽  
pp. H978-H985 ◽  
Author(s):  
Takafumi Iesaki ◽  
Sachin A. Gupte ◽  
Pawel M. Kaminski ◽  
Michael S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Superoxide Production ◽  
No Donor ◽  
Arterial Relaxation ◽  
Stimulation Of

The inhibitor of soluble guanylate cyclase (sGC) stimulation by nitric oxide (NO), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), was examined for its effects on the prolonged relaxation of endothelium-removed bovine coronary (BCA) and pulmonary (BPA) arteries to peroxynitrite (ONOO−) and on H2O2-elicited relaxation and sGC stimulation. Our previous studies suggest that ONOO− causes a prolonged relaxation of BPA by regenerating NO and that a 2-min exposure of BCA or BPA to 50 nM NO causes an ONOO−-elicited relaxation. The relaxation of K+-precontracted BCA to 50 nM NO or 100 μM ONOO− was essentially eliminated by 10 μM ODQ. ODQ also eliminated relaxation to 0.1 nM-10 μM of NO donor S-nitroso- N-acetyl-penicillamine (SNAP), but it did not alter relaxation to 1–300 μM H2O2. Similar responses were also observed in BPA. ODQ did not increase lucigenin-detectable superoxide production in BCA, and it did not alter luminol-detectable endogenous ONOO− formation observed during a 2-min exposure of BCA to 50 nM NO. In addition, ODQ did not affect tissue release of NO after 2 min exposure of BCA to 50 nM NO. The activity of sGC in BPA homogenate that is stimulated by endogenous H2O2was not altered by ODQ, whereas sGC activity in the presence of 10 μM SNAP (+fungal catalase) was reduced by ODQ. Thus relaxation of K+-precontracted BCA and BPA to ONOO− appears to be completely mediated by NO stimulation of sGC, whereas the actions of ODQ suggest that NO is not involved in H2O2-elicited relaxation and sGC stimulation. This study did not detect evidence for the participation of additional mechanisms potentially activated by ONOO− in the responses studied.

Regulation of NHE3 by nitric oxide in Caco-2 cells

2002 ◽  
Vol 283 (3) ◽  
pp. G747-G756 ◽  
Author(s):  
Ravinder K. Gill ◽  
Seema Saksena ◽  
Irfan Ali Syed ◽  
Sangeeta Tyagi ◽  
Waddah A. Alrefai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Signal Transduction Pathway ◽  
Specific Protein ◽  
Protein Kinase G ◽  
Kinase A ◽  
Specific Protein Kinase

The effect of nitric oxide (NO) on Na+/H+ exchange (NHE) activity was investigated utilizing Caco-2 cells as an experimental model. Incubation of Caco-2 cells with 10−3 M S-nitroso- N-acetylpenicillamine (SNAP), a conventional donor of NO, for 20 min resulted in a ∼45% dose-dependent decrease in NHE activity, as determined by assay of ethylisopropylamiloride-sensitive 22Na uptake. A similar decrease in NHE activity was observed utilizing another NO-specific donor, sodium nitroprusside. SNAP-mediated inhibition of NHE activity was not secondary to a loss of cell viability. NHE3 activity was significantly reduced by SNAP ( P < 0.05), whereas NHE2 activity was essentially unaltered. The effects of SNAP were mediated by the cGMP-dependent signal transduction pathway as follows: 1) LY-83583 and 1 H-(1,2,4)oxadiazolo(4,3- a)quinoxalin-1-one (ODQ), specific inhibitors of soluble guanylate cyclase, blocked the inhibitory effect of SNAP on NHE; 2) 8-bromo-cGMP mimicked the effects of SNAP on NHE activity; 3) the SNAP-induced decrease in NHE activity was counteracted by a specific protein kinase G inhibitor, KT-5823 (1 μM); 4) chelerythrine chloride (2 μM) or calphostin C (200 nM), specific protein kinase C inhibitors, did not affect inhibition of NHE activity by SNAP; 5) there was no cross activation by the protein kinase A-dependent pathway, as the inhibitory effects of SNAP were not blocked by Rp-cAMPS (25 μM), a specific protein kinase A inhibitor. These data provide novel evidence that NO inhibits NHE3 activity via activation of soluble guanylate cyclase, resulting in an increase in intracellular cGMP levels and activation of protein kinase G.

scholarly journals Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide

2008 ◽  
Vol 294 (3) ◽  
pp. H1244-H1250 ◽  
Author(s):  
Christopher J. Mingone ◽  
Mansoor Ahmad ◽  
Sachin A. Gupte ◽  
Joseph L. Chow ◽  
Michael S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Organ Culture ◽  
Heme Oxygenase ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Heme Oxygenase 1 ◽  
No Donor ◽  
Spermine Nonoate

This study examines in endothelium-denuded bovine pulmonary arteries the effects of increasing heme oxygenase-1 (HO-1) activity on relaxation and soluble guanylate cyclase (sGC) activation by nitric oxide (NO). A 24-h organ culture with 0.1 mM cobalt chloride (CoCl2) or 30 μM Co-protoporphyrin IX was developed as a method of increasing HO-1 expression. These treatments increased HO-1 expression and HO activity by approximately two- to fourfold and lowered heme levels by 40–45%. Induction of HO-1 was associated with an attenuation of pulmonary arterial relaxation to the NO-donor spermine-NONOate. The presence of a HO-1 inhibitor 30 μM chromium mesoporphyrin during the 24-h organ culture (but not acute treatment with this agent) reversed the attenuation of relaxation to NO seen in arteries co-cultured with agents that increased HO-1. Relaxation to isoproterenol, which is thought to be mediated through cAMP, was not altered in arteries with increased HO-1. Inducers of HO-1 did not appear to alter basal sGC activity in arterial homogenates or expression of the β1-subunit of sGC. However, the increase in activity seen in the presence of 1 μM spermine-NONOate was attenuated in homogenates obtained from arteries with increased HO-1. Since arteries with increased HO-1 had decreased levels of superoxide detected by the chemiluminescence of 5 μM lucigenin, superoxide did not appear to be mediating the attenuation of relaxation to NO. These data suggest that increasing HO-1 activity depletes heme, and this is associated with an attenuation of pulmonary artery relaxation and sGC activation responses to NO.

Nitric oxide acts independently of cGMP to modulate capacitative Ca2+ entry in mouse parotid acini

1999 ◽  
Vol 277 (2) ◽  
pp. C262-C270 ◽  
Author(s):  
Eileen L. Watson ◽  
Kerry L. Jacobson ◽  
Jean C. Singh ◽  
Sabrina M. Ott
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guanylate Cyclase ◽  
Feedback Loop ◽  
Soluble Guanylate Cyclase ◽  
Complete Inhibition ◽  
No Donor ◽  
Nos Inhibitors ◽  
Induced Changes ◽  
Oxide Synthase

Carbachol- and thapsigargin-induced changes in cGMP accumulation were highly dependent on extracellular Ca2+ in mouse parotid acini. Inhibition of nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) resulted in complete inhibition of agonist-induced cGMP levels. NOS inhibitors reduced agonist-induced Ca2+ release and capacitative Ca2+ entry, whereas the inhibition of sGC had no effect. The effects of NOS inhibition were not reversed by 8-bromo-cGMP. The NO donor GEA-3162 increased cGMP levels blocked by the inhibition of sGC. GEA-3162-induced increases in Ca2+ release from ryanodine-sensitive stores and enhanced capacitative Ca2+ entry, both of which were unaffected by inhibitors of sGC but reduced by NOS inhibitors. Results support a role for NO, independent of cGMP, in agonist-mediated Ca2+release and Ca2+ entry. Data suggest that agonist-induced Ca2+influx activates a Ca2+-dependent NOS, leading to the production of NO and the release of Ca2+ from ryanodine-sensitive stores, providing a feedback loop by which store-depleted Ca2+ channels are activated.

NADPH and heme redox modulate pulmonary artery relaxation and guanylate cyclase activation by NO

1999 ◽  
Vol 277 (6) ◽  
pp. L1124-L1132 ◽  
Author(s):  
Sachin A. Gupte ◽  
Tasneem Rupawalla ◽  
Donald Phillibert ◽  
Michael S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Redox Status ◽  
Pentose Phosphate ◽  
Inhibitory Effects ◽  
No Donor ◽  
Guanylate Cyclase Activation ◽  
Stimulation Of

The hemoprotein oxidant ferricyanide (FeCN) converts the iron of the heme on soluble guanylate cyclase (sGC) from Fe2+ to Fe3+, which prevents nitric oxide (NO) from binding the heme and stimulating sGC activity. This study uses FeCN to examine whether modulation of the redox status of the heme on sGC influences the relaxation of endothelium-removed bovine pulmonary arteries (BPA) to NO. Pretreatment of the homogenate of BPA with 50 μM FeCN resulted in a loss of stimulation of sGC activity by the NO donor 10 μM S-nitroso- N-acetylpenicillamine (SNAP). In the FeCN-treated homogenate reconcentrated to the enzyme levels in BPA, 100 μM NADPH restored NO stimulation of sGC, and this effect of NADPH was prevented by an inhibitor of flavoprotein electron transport, 1 μM diphenyliodonium (DPI). In BPA the relaxation to SNAP was not altered by FeCN, inhibitors of NADPH generation by the pentose phosphate pathway [250 μM 6-aminonicotinamide (6-AN) and 100 μM epiandrosterone (Epi)], or 1 μM DPI. However, the combination of FeCN with 6-AN, Epi, or DPI inhibited ( P < 0.05) relaxation to SNAP without significantly altering the relaxation of BPA to forskolin. The inhibitory effects of 1 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (a probe that appears to convert NO-heme of sGC to its Fe3+-heme form) on relaxation to SNAP were also enhanced by DPI. These observations suggest that a flavoprotein containing NADPH oxidoreductase may influence cGMP-mediated relaxation of BPA to NO by maintaining the heme of sGC in its Fe2+ oxidation state.

scholarly journals Soluble Guanylate Cyclase As the Key Enzyme in the Modulating Effect of NO on Metabotropic Glutamate Receptors

Acta Naturae ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 71-78 ◽  
Author(s):  
I. V. Ryzhova ◽  
A. D. Nozdrachev ◽  
T. V. Tobias ◽  
E. A. Vershinina
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptors ◽  
Guanylate Cyclase ◽  
Metabotropic Glutamate Receptors ◽  
Soluble Guanylate Cyclase ◽  
Background Activity ◽  
Specific Inhibitor ◽  
No Donor ◽  
Metabotropic Glutamate ◽  
Afferent Synapse

The synaptic plasticity of the afferent synapse of the vestibular apparatus is defined by the dynamic interaction of ionotropic and metabotropic glutamate receptors and the modulators of synaptic transmission. It was shown that nitric oxide modulates iGluR responses. In this paper, the effect of NO on the function of the afferent synapse mGluR was investigated. Inhibitor of nitric oxide synthase lowered the level of background activity but increased the amplitude of the responses of groups I and II mGluR agonist ACPD. Donor NO SNAP increased the level of background activity. Short-term perfusion of the synaptic region with low concentrations of SNAP led to a decrease in the amplitude of the answers of mGluR agonists ACPD and DHPG. The inhibitory effect of the NO donor was eliminated under blockade of soluble guanylate cyclase with a specific inhibitor ODQ. A prolonged application of NO did not cause a statistically significant change in the amplitude of the ACPD response. However, SNAP at concentrations of 10 and 100 M increased the amplitude of the mGluR agonist responses 30 and 15 minutes, respectively, after termination of the NO donor exposure. The obtained data show the multidirectional effect of NO on the function of mGluR and testify to the existence of a complex modulating mechanism of the afferent flow from vestibular organs to the central nervous system.

Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway

2007 ◽  
Vol 292 (2) ◽  
pp. H893-H903 ◽  
Author(s):  
Galina N. Antonova ◽  
Connie M. Snead ◽  
Alexander S. Antonov ◽  
Christiana Dimitropoulou ◽  
Richard C. Venema ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Injury ◽  
Soluble Guanylate Cyclase ◽  
Heat Shock Protein 90 ◽  
Protective Effects ◽  
No Donor ◽  
Spermine Nonoate

Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)- N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 μM SNP, 10 μM spermine NONOate, or 100 μM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 μM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.

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