scholarly journals Dopamine in the ink defence system of Sepia officinalis: biosynthesis, vesicular compartmentation in mature ink gland cells, nitric oxide (NO)/cGMP-induced depletion and fate in secreted ink1

2004 ◽  
Vol 378 (3) ◽  
pp. 785-791 ◽  
Author(s):  
Gabriella FIORE ◽  
Annarita POLI ◽  
Anna Di COSMO ◽  
Marco d'ISCHIA ◽  
Anna PALUMBO
Keyword(s):  
Nitric Oxide ◽  
Tyrosine Hydroxylase ◽  
Physical Adsorption ◽  
Signalling Pathway ◽  
Nitric Oxide Donor ◽  
Sepia Officinalis ◽  
Release Process ◽  
No Donor ◽  
Cgmp Signalling ◽  
Incubation Experiments

The biosynthesis, localization and fate of catecholamines in the ink gland of the cuttlefish Sepia officinalis were investigated by combined biochemical and immunohistocytochemical methodologies. HPLC analysis of crude ink gland extracts indicated the presence of dopa (2.18±0.82 nmol/mg of protein) and DA (dopamine, 0.06±0.02 nmol/mg of protein), but no detectable noradrenaline or adrenaline. DA was shown to derive from l-tyrosine, according to experiments performed by incubating intact ink glands with [l-14C]tyrosine. The biosynthetic process involves a tyrosine hydroxylase and a dopa decarboxylase pathway and is independent of tyrosinase. The tyrosine hydroxylase activity was detected under conditions of tyrosinase suppression in the cytosolic fraction, but not in the melanosomal fraction, of ink gland extracts, and the presence of the enzyme was confirmed by Western-blot analysis. Dopa and DA were found to be released from the ink glands by processes controlled through the NMDA-nitric oxide-cGMP (where NMDA stands for N-methyl-d-aspartate) signalling pathway, as apparent from incubation experiments performed with [l-14C]tyrosine in the presence of NMDA, diethylamine NONOate (diethylamine diazeniumdiolate), a nitric oxide donor, 8-bromo-cGMP or a guanylyl cyclase inhibitor. Immunohistochemical results coupled with electron microscopy indicated that DA was concentrated in vesicles specifically localized in the mature melanin-producing cells of the ink gland proximal to the lumen and separated from the melanin-containing melanosomes. NMDA receptor stimulation or exposure to an NO donor caused a marked loss of DA immunoreactivity in mature cells, consistent with a release process. In the lumen of the ink gland, where mature exhausted cells pour their contents, DA immunoreactivity was found to be associated with the melanin granules, due apparently to physical adsorption. Overall, these results point to DA as a marker of cell maturation in Sepia ink gland subject to release by the NO/cGMP signalling pathway, and disclose apparently overlooked DA–melanin interactions in secreted ink of possible relevance to the defence mechanism.

Nitric-oxide-dependent activation of pig oocytes: the role of the cGMP-signalling pathway

Zygote ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 9-16 ◽  
Author(s):  
J. Petr ◽  
R. Rajmon ◽  
E. Chmelíková ◽  
M. Tománek ◽  
V. Lánská ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Specific Inhibitor ◽  
Calcium Ionophore ◽  
Signalling Pathway ◽  
Nitric Oxide Donor ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Oocyte Activation ◽  
No Donor

Pig oocytes matured in vitro were parthenogenetically activated (78%) after treatment with 2 mM nitric oxide-donor (±)-S-nitroso-N-acetylpenicillamine (SNAP) for 24 h. Inhibition of soluble guanylyl cyclase with the specific inhibitors 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 6-anilino-5,8-quinolinequinone (LY83583) suppressed the SNAP-induced activation in a dose-dependent manner (23% of activated oocytes after treatment with 400 μM ODQ; 12% of activated oocytes after treatment with 40 μM LY83583). 8-Bromo-cyclic guanosine monophosphate (8-Br-cGMP), a phosphodiesterase-resistant analogue of cGMP, enhances the effect of suboptimal doses (0.1 or 0.5 mM) of the NO donor SNAP. DT3, a specific inhibitor of cGMP-dependent protein kinase (PKG, PKG), is also able to inhibit the activation of pig oocytes after NO donor treatment. Involvement of the cGMP-dependent signalling pathway is specific for NO-induced oocyte activation, because both the guanylyl cyclase inhibitor ODQ and the PKG inhibitor DT3 are unable to inhibit activation in oocytes treated with the calcium ionophore A23187. These data indicate that the activation of pig oocytes with an NO donor is cGMP-dependent and that PKG plays an important role in this mode of oocyte activation.

Skeletal muscle force and actomyosin ATPase activity reduced by nitric oxide donor

1997 ◽  
Vol 83 (4) ◽  
pp. 1326-1332 ◽  
Author(s):  
William J. Perkins ◽  
Young-Soo Han ◽  
Gary C. Sieck
Keyword(s):  
Nitric Oxide ◽  
Mechanical Properties ◽  
Atpase Activity ◽  
Muscle Force ◽  
Isometric Force ◽  
Nitric Oxide Donor ◽  
No Donor ◽  
Single Fibers ◽  
Actomyosin Atpase ◽  
Cross Bridge

Perkins, William J., Young-Soo Han, and Gary C. Sieck.Skeletal muscle force and actomyosin ATPase activity reduced by nitric oxide donor. J. Appl. Physiol.83(4): 1326–1332, 1997.—Nitric oxide (NO) may exert direct effects on actin-myosin cross-bridge cycling by modulating critical thiols on the myosin head. In the present study, the effects of the NO donor sodium nitroprusside (SNP; 100 μM to 10 mM) on mechanical properties and actomyosin adenosinetriphosphatase (ATPase) activity of single permeabilized muscle fibers from the rabbit psoas muscle were determined. The effects of N-ethylmaleimide (NEM; 5–250 μM), a thiol-specific alkylating reagent, on mechanical properties of single fibers were also evaluated. Both NEM (≥25 μM) and SNP (≥1 mM) significantly inhibited isometric force and actomyosin ATPase activity. The unloaded shortening velocity of SNP-treated single fibers was decreased, but to a lesser extent, suggesting that SNP effects on isometric force and actomyosin ATPase were largely due to decreased cross-bridge recruitment. The calcium sensitivity of SNP-treated single fibers was also decreased. The effects of SNP, but not NEM, on force and actomyosin ATPase activity were reversed by treatment with 10 mMdl-dithiothreitol, a thiol-reducing agent. We conclude that the NO donor SNP inhibits contractile function caused by reversible oxidation of contractile protein thiols.

scholarly journals Synthesis and characterization of a fluorinated S-nitrosothiol as the nitric oxide donor for fluoropolymer-based biomedical device applications

2018 ◽  
Vol 6 (38) ◽  
pp. 6142-6152 ◽  
Author(s):  
Yang Zhou ◽  
Qi Zhang ◽  
Jianfeng Wu ◽  
Chuanwu Xi ◽  
Mark E. Meyerhoff
Keyword(s):  
Nitric Oxide ◽  
Polyvinylidene Fluoride ◽  
Nitric Oxide Donor ◽  
Synthesis And Characterization ◽  
No Donor ◽  
Fluorinated Polymer ◽  
Biomedical Device ◽  
Device Applications

The first nitric oxide (NO) releasing fluorinated polymer was developed via incorporating a new fluorinated NO donor into polyvinylidene fluoride tubing.

Nitric oxide donor stimulated increase of cyclic GMP in the goldfish retina

2001 ◽  
Vol 18 (6) ◽  
pp. 849-856 ◽  
Author(s):  
WILLIAM H. BALDRIDGE ◽  
ANDY J. FISCHER
Keyword(s):  
Nitric Oxide ◽  
Optic Nerve ◽  
Ganglion Cells ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Nitric Oxide Donor ◽  
No Donor ◽  
Intracellular Signalling Pathway ◽  
Teleost Retina

Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) and the resulting increase in cyclic guanosine monophosphate (cGMP) is an important intracellular signalling pathway in the vertebrate retina. Immunocytochemical detection of cGMP following exposure to NO donors has proven an effective method of identifying cells that express sGC. While such an approach has proven useful for the study of several vertebrate retinas, it has not been applied to the well-characterized teleost retina. Therefore, in the present study, we have applied this approach to the retina of the goldfish (Carassius auratus). In the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), incubation of goldfish eyecups in Ringer's solution containing (±)-S-nitroso-N-acetylpenicillamine (SNAP) increased cGMP-like immunoreactivity (cG-ir) in bipolar, horizontal, amacrine, and ganglion cells and in ganglion cell axons and optic nerve. Weak labeling was observed in horizontal cells but no change in cG-ir was noted within photoreceptors. The NO donor-stimulated increases of cG-ir in horizontal, bipolar, amacrine, and ganglion cells are consistent with known physiological effects of NO on these neurons. The physiological significance of NO action at the level of optic nerve is not known. The lack of an effect of SNAP on cG-ir in photoreceptors was unexpected, as there are known physiological actions of NO, mediated by cGMP, on these neurons. Although this may be due to insufficient sensitivity of immunolabeling, this result may indicate a difference between isoforms of sGC or cGMP PDE in these neurons, compared to neurons where exogenous NO increased cG-ir.

scholarly journals Local infusion of the nitric oxide donor sin-1 after angioplasty: Effects on intimal hyperplasia in porcine coronary arteries

2003 ◽  
Vol 44 (4) ◽  
pp. 395-402
Author(s):  
J. Harnek ◽  
E. Zoucas ◽  
R. Sjuve ◽  
A. Arner ◽  
E. Ekblad ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Intimal Hyperplasia ◽  
Percutaneous Transluminal Coronary Angioplasty ◽  
Local Delivery ◽  
Nitric Oxide Donor ◽  
Histological Evaluation ◽  
No Donor ◽  
Luminal Diameter ◽  
Transluminal Coronary Angioplasty

Purpose: To investigate the development of intimal hyperplasia in response to percutaneous transluminal coronary angioplasty (PTCA) followed by local delivery of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1). Material and Methods: Overdilation PTCA was performed in coronary arteries in 20 healthy pigs. One of the dilated segments was additionally treated with local delivery of SIN-1 for 10 min. Segments distal to the treated part of the arteries served as controls. Arteries were radiographically depicted and analyzed after 1 and 8 weeks for actin, myosin and intermediate filaments (IF), nitric oxide synthetase (NOS) and histological evaluation. Results: Segments treated with PTCA+SIN-1 showed a significantly ( p = 0.03) larger luminal diameter compared with PTCA only treated segments. The luminal loss after SIN-1 was not significant compared with the diameter prior to treatment. Endothelial NOS content was significantly lower in the PTCA+SIN-1 group compared with the PTCA group after 1 ( p = 0.03) and 8 weeks ( p = 0.013). IF/actin ratio after 1 week was significantly increased in PTCA-treated segments compared with untreated controls ( p = 0.004), and compared with PTCA+SIN-1-treated segments ( p = 0.004). Conclusion: PTCA-induced intimal hyperplasia was potently inhibited by local delivery of the NO donor SIN-1. Momentary events at the time of injury play a significant role in the development of intimal hyperplasia and long-lasting down-regulation of the endothelial NOS expression after SIN-1 exposure is suggested. The IF/actin ratio can be useful as an early marker of intimal hyperplasia.

The nitric oxide donor molsidomine rescues cardiac function in rats with chronic kidney disease and cardiac dysfunction

2010 ◽  
Vol 299 (6) ◽  
pp. H2037-H2045 ◽  
Author(s):  
Lennart G. Bongartz ◽  
Branko Braam ◽  
Marianne C. Verhaar ◽  
Maarten Jan M. Cramer ◽  
Roel Goldschmeding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
No Synthase ◽  
Nitric Oxide Donor ◽  
No Production ◽  
No Donor

We recently developed a rat model of cardiorenal failure that is characterized by severe left ventricular systolic dysfunction (LVSD) and low nitric oxide (NO) production that persisted after temporary low-dose NO synthase inhibition. We hypothesized that LVSD was due to continued low NO availability and might be reversed by supplementing NO. Rats underwent a subtotal nephrectomy and were treated with low-dose NO synthase inhibition with Nω-nitro-l-arginine up to week 8. After 3 wk of washout, rats were treated orally with either the long-acting, tolerance-free NO donor molsidomine (Mols) or vehicle (Veh). Cardiac and renal function were measured on weeks 11, 13, and 15. On week 16, LV hemodynamics and pressure-volume relationships were measured invasively, and rats were killed to quantify histological damage. On week 15, blood pressure was mildly reduced and creatinine clearance was increased by Mols (both P < 0.05). Mols treatment improved ejection fraction (53 ± 3% vs. 37 ± 2% in Veh-treated rats, P < 0.001) and stroke volume (324 ± 33 vs. 255 ± 15 μl in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 ± 1.1 mmHg) than Veh-treated rats (16.3 ± 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 ± 1.8 vs. 30.9 ± 3.3 ms, respectively, P < 0.05). The LV end-systolic pressure-volume relationship was shifted to the left in Mols compared with Veh treatment. In summary, in a model of cardiorenal failure with low NO availability, supplementing NO significantly improves cardiac systolic and diastolic function without a major effect on afterload.

Abstract 13295: Novel Experimental Therapeutics for COVID-19 Derived From a Nitric Oxide Donor

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
John F Schmedtje ◽  
Zahra Assar
Keyword(s):  
Nitric Oxide ◽  
Protein Interactions ◽  
In Silico ◽  
Vascular Endothelial Cells ◽  
Specific Binding ◽  
Nitric Oxide Donor ◽  
Isosorbide Mononitrate ◽  
Vascular Endothelial ◽  
No Donor ◽  
Glide Docking

Urea transport protein B, the product of the gene SLC14A1 , facilitates transport of urea, water and urea analogues across cell membranes. SLC14A1 mRNA is overexpressed in human vascular endothelial cells in culture under hypoxic (1% oxygen) conditions compared with normoxia. This leads to transport of urea out of the endothelial cell and likely contributes to the reduction in eNOS (endothelial nitric oxide synthase) pathway activity in hypoxia. NO has antiviral activity. Novel compounds were developed by binding a urea-like moiety to the backbone of the generic agent isosorbide mononitrate, a well-known NO donor, to combat vascular endothelial dysfunction in COVID-19, a disease characterized by systemic hypoxia and inflammation due to SARS-CoV-2 infection. A study of drug-protein interactions was undertaken using in silico modelling. Novel compounds were studied against 9 key SARS-CoV-2 targets using Maestro, Schrödinger Suite software (Glide docking). Docking scores and intermolecular interactions within the target’s key binding amino acid residues were studied to compare investigational compounds and known antivirals. Several novel agents tested had a better Glide Score (a prediction of ligand affinity) against the papain-like protease (PL pro ) of SARS-CoV-2 compared with known antiviral drugs. PL pro is considered to be a primary target for therapeutic inhibition of the SARS viruses. The candidate compounds CR-305, CR-607, CR-510 and CR-605 were all superior to Remdesivir, GS-441524, Lopinavir, Boceprevir, and Ribavirin. Given the known direct antiviral action of NO and evidence of specific binding of these compounds to the PL pro of SARS-CoV-2 based on the in silico results, we conclude there is a high likelihood these novel compounds will prove to be of therapeutic value against COVID-19. CR-305 appears to have a higher affinity to SARS-CoV-2 than other antivirals as it sits firmly in the PL pro catalytic pocket and makes the most of key interactions with the catalytic pocket residues: Gly163, Asp164, Gln271 and Tyr264. These data call for a new focus on these novel antiviral agents as they appear to bind with an increased avidity to PL pro (compared with other known antivirals) while targeting delivery of NO to the SARS-CoV-2 virus in COVID-19.

Nitric oxide induces epidermal stem cell de-adhesion by targeting integrin β1 and Talin via the cGMP signalling pathway

Nitric Oxide ◽  
2018 ◽  
Vol 78 ◽  
pp. 1-10 ◽  
Author(s):  
Rixing Zhan ◽  
Fan Wang ◽  
Ying Wu ◽  
Ying Wang ◽  
Wei Qian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Signalling Pathway ◽  
Epidermal Stem Cell ◽  
Integrin Β1 ◽  
Cgmp Signalling

scholarly journals Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle

2002 ◽  
Vol 282 (5) ◽  
pp. H1787-H1792 ◽  
Author(s):  
Moshe Swissa ◽  
Toshihiko Ohara ◽  
Moon-Hyoung Lee ◽  
Sanjay Kaul ◽  
Prediman K. Shah ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Donor ◽  
Tyrode Solution ◽  
No Donor ◽  
Maximum Slope ◽  
No Donors ◽  
Restitution Curve ◽  
Rapid Pacing ◽  
Drug Free ◽  
Endocardial Activation

We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced. Sildenafil (0.2 μg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 μg/ml sildenafil was combined with NO donors, the incidence of VT and VF rose significantly ( P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects of sildenafil were reversible after drug-free Tyrode solution perfusion. We conclude that a sildenafil (2 μg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis.

Actions of a nitric oxide donor on prostaglandin production and angiogenic activity in the equine endometrium

2008 ◽  
Vol 20 (6) ◽  
pp. 674 ◽  
Author(s):  
Rosário P. Roberto da Costa ◽  
Ana S. Costa ◽  
Anna J. Korzekwa ◽  
Rafal Platek ◽  
Marta Siemieniuch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
In Vitro Release ◽  
Oestrous Cycle ◽  
Nitric Oxide Donor ◽  
Bovine Aortic Endothelial Cell ◽  
Prostaglandin E ◽  
No Production ◽  
No Donor ◽  
Angiogenic Activity ◽  
Prostaglandin Production

Nitric oxide (NO) plays an important role in prostaglandin secretion and angiogenesis in the reproductive system. In the present study, the roles of the NO donor spermine NONOate and tumour necrosis factor-α (TNF; as a positive control) in prostaglandin production and angiogenic activity of equine endometria during the oestrous cycle were evaluated. In addition, the correlation between NO production and the expression of key prostaglandin synthase proteins was determined. The protein expression of prostaglandin F synthase (PGFS) increased in early and mid-luteal stages, whereas that of prostaglandin E synthase (PGES) was increased in the early luteal stage. The in vitro release of NO was highest after ovulation. There was a high correlation between NO production and PGES expression, as well as NO release and PGFS expression. There were no differences detected in prostaglandin H synthase 2 (PTGS-2) throughout the oestrous cycle and there was no correlation between PTGS-2 expression and NO. In TNF- or spermine-treated endometria, the expression of prostaglandin (PG) E2 increased in the early and mid-luteal phases, whereas that of PGF2α increased in the follicular and late luteal phases. Bovine aortic endothelial cell (BAEC) proliferation was stimulated in TNF-treated follicular-phase endometria. However, in spermine-treated endometria, NO delivered from its donor had no effect, or even an inhibitory effect, on BAEC proliferation. In conclusion, despite no change in PTGS-2 expression throughout the oestrous cycle in equine endometrial tissue, there were changes observed in the expression of PGES and PGFS, as well as in the production of PGE2 and PGF2α. In the mare, NO is involved in the secretory function of the endometrium, modulating PGE2 and PGF2α production. Even though TNF caused an increase in the production of angiogenic factors and prostaglandins, its complex action in mare uterus should be elucidated.

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