The Experts below are selected from a list of 507 Experts worldwide ranked by ideXlab platform
Daniel Chavarriabolanos - One of the best experts on this subject based on the ideXlab platform.
-
involvement of nitric oxide and atp sensitive potassium channels in the peripheral antinoceptive action of a tramadol dexketoprofen combination in the formalin test
Drug Development Research, 2014Co-Authors: Mario A Isiordiaespinoza, Jose Perezurizar, Daniel Chavarriabolanos, Amaury PozosguillenAbstract:Preclinical Research Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)–cyclic guanosine monophosphate pathway and ATP-sensitive K+ channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction duriNg the second phase of the formalin test. Pretreatment with NO antagonists, includiNg l-Ng-Nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K+ channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol–dexketoprofen combination, suggestiNg that NO and ATP-sensitive K+ channels were involved.
Geoffrey Burnstock - One of the best experts on this subject based on the ideXlab platform.
-
effects of nitric oxide synthase inhibitors l Ng Nitroarginine and l Ng Nitroarginine methyl ester on responses to vasodilators of the guinea pig coronary vasculature
British Journal of Pharmacology, 1992Co-Authors: Amanda J Vials, Geoffrey BurnstockAbstract:1. The effects of L-Ng-Nitroarginine (L-NOARG) and L-Ng-Nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a LaNgendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibitiNg the vasodilator actions of 5-HT and ATP in this preparation.
Irmgard Tegeder - One of the best experts on this subject based on the ideXlab platform.
-
Protein S-nitrosylation and denitrosylation in the mouse spinal cord upon injury of the sciatic nerve.
Journal of proteomics, 2012Co-Authors: Reynir Scheving, Ilka Wittig, Heinrich Heide, Boris Albuquerque, Mirco Steger, Ulrich Brandt, Irmgard TegederAbstract:Nitric oxide is a pain signaliNg molecule and exerts its influence through two primary pathways: by stimulation of soluble guanylylcyclase and by direct S-nitrosylation (SNO) of target proteins. We assessed in the spinal cord the SNO-proteome with two methods, two-dimensional S-nitrosothiol difference gel electrophoresis (2D SNO-DIGE) and SNO-site identification (SNOSID) at baseline and 24h after sciatic nerve injury with/without pretreatment with the nitric oxide synthase inhibitor L-Ng-Nitroarginine methyl ester (L-NAME). After nerve injury, SNO-DIGE revealed 30 proteins with increased and 23 proteins with decreased S-nitrosylation. SNO-sites were identified for 17 proteins. After sham surgery only 3 proteins were up-nitrosylated. L-NAME pretreatment substantially reduced both constitutive and nerve injury evoked up-S-nitrosylation. For the top candidates S-nitrosylation was confirmed with the biotin switch technique and time course analyses at 1 and 7days showed that SNO modifications of protein disulfide isomerase, glutathione synthase and peroxiredoxin-6 had returned to baseline within 7days whereas S-nitrosylation of mitochondrial aconitase 2 was further increased. The identified SNO modified proteins are involved in mitochondrial function, protein foldiNg and transport, synaptic signaliNg and redox control. The data show that nitric oxide mediated S-nitrosylation contributes to the nerve injury-evoked pathology in nociceptive signaliNg pathways.
Mario A Isiordiaespinoza - One of the best experts on this subject based on the ideXlab platform.
-
involvement of nitric oxide and atp sensitive potassium channels in the peripheral antinoceptive action of a tramadol dexketoprofen combination in the formalin test
Drug Development Research, 2014Co-Authors: Mario A Isiordiaespinoza, Jose Perezurizar, Daniel Chavarriabolanos, Amaury PozosguillenAbstract:Preclinical Research Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)–cyclic guanosine monophosphate pathway and ATP-sensitive K+ channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction duriNg the second phase of the formalin test. Pretreatment with NO antagonists, includiNg l-Ng-Nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K+ channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol–dexketoprofen combination, suggestiNg that NO and ATP-sensitive K+ channels were involved.
Shashi Bala Singh - One of the best experts on this subject based on the ideXlab platform.
-
neuroprotective role of l Ng Nitroarginine methyl ester l name against chronic hypobaric hypoxia with crowdiNg stress chc induced depression like behaviour
PLOS ONE, 2016Co-Authors: Satya Narayan Deep, I Baitharu, Dipti Prasad, Apurva Sharma, Anoop Kishor Singh Gurjar, Shashi Bala SinghAbstract:Improper neuroimmune responses followiNg chronic stress exposure have been reported to cause neuronal dysfunctions leadiNg to memory impairment, anxiety and depression like behaviours. Though several factors affectiNg microglial activation and consequent alteration in neuro-inflammatory responses have been well studied, role of NO and its association with microglia in stress induced depression model is yet to be explored. In the present study, we validated combination of chronic hypobaric hypoxia and crowdiNg (CHC) as a stress model for depression and investigated the role of chronic stress induced elevated nitric oxide (NO) level in microglia activation and its effect on neuro-inflammatory responses in brain. Further, we evaluated the ameliorative effect of L-Ng-Nitroarginine Methyl Ester (L-NAME) to reverse the stress induced depressive mood state. Four groups of male Sprague Dawley rat were taken and divided into control and CHC stress exposed group with and without treatment of L-NAME. Depression like behaviour and anhedonia in rats were assessed by Forced Swim Test (FST) and Sucrose Preference Test (SPT). Microglial activation was evaluated usiNg Iba-1 immunohistochemistry and proinflammatory cytokines were assessed in the hippocampal region. Our result showed that exposure to CHC stress increased the number of active microglia with correspondiNg increase in inflammatory cytokines and altered behavioural responses. The inhibition of NO synthesis by L-NAME duriNg CHC exposure decreased the number of active microglia in hippocampus as evident from decreased Iba-1 positive cells. Further, L-NAME administration decreased pro-inflammatory cytokines in hippocampus and improved behaviour of rats. Our study demonstrate that stress induced elevation of NO plays pivotal role in altered microglial activation and consequent neurodegenerative processes leadiNg to depression like behaviour in rat.
-
13 anti inflammatory role of l Ng Nitroarginine methyl ester in a chronic model of depression
Brain Behavior and Immunity, 2013Co-Authors: Satya Narayan Deep, Ajay K Sharma, I Baitharu, Vishal Jain, Dipti Prasad, Shashi Bala SinghAbstract:The role of nitric oxide (NO) in the neurodegenerative disorders is well illustrated. The close relationship of NO level and the inflammation points out the clinical relevance of NO in depressive disorder. Present study evaluated the neuroprotective role of L-NAME, a NO synthase blocker in chronic restraint hypoxia (CRH) induced depressive behaviour. Briefly four groups of rat were exposed to CRH for 21 days. Group 1 and 2 served as normoxic control group (NOR + VEH, NOR + DRUG), group 3 and 4 served as stress exposed groups (CRH + VEH, CRH + DRUG) and the 5th group was LPS (Lipopolysaccharide) + DRUG. On the last day behavioural assessment was done and immediately brain sample were isolated for histology and biochemical parameters. IHC, ELISA and western blot were used to study the expression of stress markers followiNg CRH exposure. Our results show that L-NAME administration to rats improved the exploratory and reariNg behaviour and also reduced despair behaviour. DCX, a marker for neuronal migration and neurogenesis was increased significantly aloNg with TRAF-2 and significant decreased in the expression of IL-1 receptor, NF-kB, iNOS, Cox-2, nNOS, H3K9 (epigenetic marker), nitric oxide and proinflammatory cytokines suggestiNg the role of L-NAME in bufferiNg the stress induced behavioural impairment. From the above study it can be concluded that L-NAME treatment improves functional outcomes of rats duriNg CRH exposure. InhibitiNg NO with L-NAME increases neurogenesis and reduces inflammation.