SB-220453, A Potential Novel Antimigraine Agent, Inhibits Nitric Oxide Release Following Induction of Cortical Spreading Depression in the Anaesthetized Cat

Cephalalgia ◽  
2000 ◽  
Vol 20 (2) ◽  
pp. 92-99 ◽  
Author(s):  
SJ Read ◽  
MI Smith ◽  
AJ Hunter ◽  
N Upton ◽  
AA Parsons
Keyword(s):  
Nitric Oxide ◽  
Median Duration ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Therapeutic Potential ◽  
Field Potential ◽  
Current Field ◽  
Nitric Oxide Release ◽  
Haemodynamic Parameters ◽  
No Release

Profound nitric oxide release associated with cortical spreading depression (SD), has been implicated in stroke, traumatic brain injury and migraine pathophysiology. SB-220453 represents a mechanistically novel, well-tolerated class of compounds which may have therapeutic potential in the treatment of conditions associated with neuronal hyperexcitability and inflammation. The aim of the present study was to investigate the effects of SB-220453 on the nitric oxide (NO) release associated with SD in the anaesthetized cat. In vehicle treated animals, KCl application for 6 min to the cortical suface produced repeated changes in extracellular direct current field potential with associated NO release. This activity was sustained for a median duration of 55 min (25–75% range, 32–59 min) and 59 min (25–75% range, 34–59 min), respectively. SB-220453 (1, 3 and 10 mg/kg i.p.) produced a dose-related inhibition of this activity and at the highest dose tested, the median duration of changes in extracellular field potential and NO release were reduced to 4 min (25–75% range, 4–5min) and 5 min (25–75% range, 5–5min), respectively. No effect was observed on basal systemic haemodynamic parameters or resting cerebral laser Doppler blood flux at any of the doses of SB-220453 tested. SB-220453 therefore represents a novel compound to assess the potential benefit of inhibiting SD associated nitric oxide release in neurological disease.

Repetitive Cortical Spreading Depression in a Gyrencephalic Feline Brain: Inhibition by the Novel Benzoylamino-Benzopyran SB-220453

Cephalalgia ◽  
2000 ◽  
Vol 20 (6) ◽  
pp. 546-553 ◽  
Author(s):  
MI Smith ◽  
SJ Read ◽  
WN Chan ◽  
M Thompson ◽  
AJ Hunter ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cortical Spreading Depression ◽  
Neurogenic Inflammation ◽  
Spreading Depression ◽  
Therapeutic Potential ◽  
The Novel ◽  
Unknown Mechanism ◽  
Nitric Oxide Release ◽  
Metabolic Coupling ◽  
Marked Inhibition

Transient cortical depolarization is implicated in the pathology of migraine. SB-220453 is a potent anti-convulsant which inhibits neurogenic inflammation and cortical spreading depression (SD)-evoked nitric oxide release via a novel but unknown mechanism. This study further investigates the effects of SB-220453 on generation and propagation of repetitive SD in the anaesthetized cat. Vehicle or SB-220453 1, 3 or 10 mg/kg was administered intraperitoneally 90 min prior to induction of SD in the suprasylvian gyrus (SG). Changes in d.c. potential were recorded in the SG and the adjacent marginal gyrus (MG). In vehicle-treated animals ( n = 7), a brief exposure (6 min) to KCl induced a median (25–75% range) number of five (four to six) and three (two to four) depolarizations over a duration of 55 min (32–59 min) and 51 min (34–58 min) in the SG and MG, respectively. SB-220453 produced dose-related inhibition of the number of events and period of repetitive SD activity. SB-220453 also reduced SD-induced repetitive pial vasodilatation but had no effect on resting haemodynamics. However, when SD events were observed in the presence of SB-220453, it had no effect on metabolic coupling. These results show that SB-220453 produces marked inhibition of repetitive SD in the anaesthetized cat. SB-220453 may therefore have therapeutic potential in treatment of SD-like activity in migraine.

Enhanced Nitric Oxide Release During Cortical Spreading Depression Following Infusion of Glyceryl Trinitrate in the Anaesthetized Cat

Cephalalgia ◽  
1997 ◽  
Vol 17 (3) ◽  
pp. 159-165 ◽  
Author(s):  
SJ Read ◽  
MI Smith ◽  
AJ Hunter ◽  
AA Parsons
Keyword(s):  
Glyceryl Trinitrate ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Nitric Oxide Release ◽  
No Release ◽  
Multiple Comparison Procedure ◽  
Post Hoc ◽  
Doppler Flux ◽  
Artery Perfusion ◽  
Perfusion Territory

Intravenous infusion of glyceryl trinitrate (GTN) into migraineurs induces an immediate headache followed by migraine. We studied the effect of GTN 10.25 g kg1 min1) on local cerebrovascular laser Doppler flux (rCBFLDF), artery diameter and NO concentration (selective NO microelectrode) in the pial middle cerebral artery perfusion territory of the anaesthetized cat, at rest and during cortical spreading depression (SD). GTN infusion induced a significant increase in pial artery diameter, rCBFLDF, and NO concentration. Following termination of infusion, NO concentrations remained significantly elevated above controls for 60 min, other parameters returned to baseliae within 10 min ( p0.05, ANOVA, post hoc Dunnett's multiple comparison procedure). Two hours after termination of infusion KCI-evoked SD was initiated. GTN-treated animals exhibited significantly ( p 0.05, Kruskal-Wallis) elevated SD-induced NO release compared to controls. All other parameters remained unaffected. Our results demonstrate that GTN induces a prolonged increase in local NO concentrations and enhances SD-induced NO release.

Retracted Article: Light-triggered nitric oxide release and targeted fluorescence imaging in tumor cells developed from folic acid-graft-carboxymethyl chitosan nanospheres

RSC Advances ◽  
2014 ◽  
Vol 4 (57) ◽  
pp. 30129-30136 ◽  
Author(s):  
Rijun Gui ◽  
Ajun Wan ◽  
Yalei Zhang ◽  
Huili Li ◽  
Tingting Zhao
Keyword(s):  
Nitric Oxide ◽  
Folic Acid ◽  
Tumor Cells ◽  
Fluorescence Imaging ◽  
Carboxymethyl Chitosan ◽  
Nitric Oxide Release ◽  
No Release ◽  
Retracted Article ◽  
Potential Applications

This article reported the synthesis of CMC–FA–RBS(CQD) nanospheres and studied their potential applications for NO release and fluorescence imaging.

scholarly journals Nitric oxide release by N-(2-chloroethyl)-N-nitrosoureas: a rarely discussed mechanistic path towards their anticancer activity

RSC Advances ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 2137-2146
Author(s):  
Amrita Sarkar ◽  
Subhendu Karmakar ◽  
Sudipta Bhattacharyya ◽  
Kallol Purkait ◽  
Arindam Mukherjee
Keyword(s):  
Nitric Oxide ◽  
Anticancer Activity ◽  
Nitric Oxide Release ◽  
No Release

Our work shows that NO release is a feasible pathway of action for aromatic and heterocyclic N-(2-chloroethyl)-N-nitrosoureas and faster NO release may not lead to higher cytotoxicity.

Nitric oxide and prostaglandins interact to mediate arteriolar dilation during cortical spreading depression

1995 ◽  
Vol 269 (1) ◽  
pp. H176-H181 ◽  
Author(s):  
W. Meng ◽  
D. M. Colonna ◽  
J. R. Tobin ◽  
D. W. Busija
Keyword(s):  
Nitric Oxide ◽  
Cortical Spreading Depression ◽  
Brain Cortex ◽  
Spreading Depression ◽  
Inhibitory Effect ◽  
Onset Latency ◽  
Cranial Window ◽  
Pial Arterioles ◽  
Oxide Synthase ◽  
Arteriolar Diameter

We examined whether blockade of prostaglandin synthesis by indomethacin could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the cerebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diameter, and NOS activity was determined by the conversion assay of [14C]arginine to [14C]citrulline. CSD dilated pial arterioles by 47 +/- 3% (baseline = 80-88 microns) (n = 21, P < 0.05), and inhibition of NOS by NG-nitro-L-arginine (L-NNA) (15 mg/kg iv) reduced dilation during CSD by over one-half (n = 8, P < 0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg iv), CSD dilated arterioles from 73 +/- 2 to 152 +/- 6 microns (n = 4, P < 0.05). However, after administration of both indomethacin and L-NNA (n = 5), CSD-induced arteriolar dilation was not different from the situation where indomethacin alone was given. Thus indomethacin completely abolished the inhibitory effect of L-NNA on CSD-induced dilation. Administration of L-NNA inhibited NOS activity in brain cortex almost completely (n = 8, P < 0.05), whereas indomethacin itself had no effect (n = 8). In addition, L-NNA inhibited topical acetylcholine (10(-5) M)-induced arteriolar dilation (n = 3, P < 0.05), and this effect was not altered by indomethacin (n = 4). In summary, L-NNA reduced arteriolar dilation during CSD. However, after administration of indomethacin, L-NNA does not reduce CSD-induced arteriolar dilation.

Asenapine modulates nitric oxide release and calcium movements in cardyomyoblasts

2016 ◽  
Vol 33 (S1) ◽  
pp. S553-S553
Author(s):  
P. Zeppegno ◽  
C. Gramaglia ◽  
E. Gattoni ◽  
S. Gili ◽  
E. Gambaro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Clinical Relevance ◽  
Nitric Oxide Release ◽  
No Release ◽  
Intracellular Ca ◽  
Specific Receptors ◽  
Competing Interest ◽  
Dopaminergic Antagonists ◽  
Serotoninergic Receptors

ObjectiveTo examine the effects of asenapine on NO release and Ca2+ transients in H9C2, which were either subjected to peroxidation or not.Materials and methodsH9C2 were treated with asenapine alone or in presence of intracellular kinases blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes.ResultsIn H9C2, asenapine differently modulated NO release and Ca2+ movements depending on the peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors and voltage Ca2+ channels blockers.ConclusionsOn the basis of our findings we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance, when considering their role in cardiac function modulation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Direct measurement of nitric oxide release from vascular endothelial cells

1996 ◽  
Vol 81 (2) ◽  
pp. 774-779 ◽  
Author(s):  
J. P. Guo ◽  
T. Murohara ◽  
M. Buerke ◽  
R. Scalia ◽  
A. M. Lefer
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Methyl Ester ◽  
Vascular Endothelial Cells ◽  
Calmodulin Antagonist ◽  
Nitric Oxide Release ◽  
A 23187 ◽  
No Release ◽  
Basal Release ◽  
Isolated Rat

A nitric oxide (NO)-selective electrode was used to directly measure NO release from isolated rat aortic endothelium and cultured rat aortic endothelial cells (RAECs). Basal release of NO was significantly attenuated by a NO synthase inhibitor NG-nitro-L-arginine methyl ester (1 mM) to 42 +/- 14 pmol/1 x 10(5) cells (P < 0.01). The basal release of NO was also significantly inhibited by a calmodulin antagonist W-7 at 15 microM (P < 0.01). L-Arginine (1 mM), significantly stimulated NO release (P < 0.05 vs. control basal release). Stimulation of cultured RAECs with two endothelium-dependent vasodilators, acetylcholine (100 nM) and A-23187 (1 microM), significantly increased NO release [574 +/- 112 pmol/1 x 10(5) cells (n = 5) and 658 +/- 119 pmol/1 x 10(5) cells (n = 5) in acetylcholine- and A-23187-stimulated RAECs, respectively]. Basal release of NO was also detectable in isolated rat aortic rings with intact endothelium. NO release was significantly attenuated by NG-nitro-L-arginine methyl ester and augmented by human superoxide dismutase. These data indicate the physiological usefulness of the amperometric measurement of NO employing a NO-specific electrode in biological systems.

scholarly journals Cerebral Blood Flow Changes during Cortical Spreading Depression are Not Altered by Inhibition of Nitric Oxide Synthesis

1994 ◽  
Vol 14 (6) ◽  
pp. 939-943 ◽  
Author(s):  
Zheng Gang Zhang ◽  
Michael Chopp ◽  
Kenneth I. Maynard ◽  
Michael A. Moskowitz
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Arterial Blood ◽  
Nos Inhibitors ◽  
Before And After ◽  
Male Wistar Rats

CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-l-arginine (L-NNA) or N-nitro-l-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO.

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