NO Signaling (no + signaling)

Distribution by Scientific Domains


Selected Abstracts


Skeletal muscle glucose uptake during exercise: A focus on reactive oxygen species and nitric oxide signaling

IUBMB LIFE, Issue 5 2009
Troy L. Merry
Abstract Like insulin, muscle contraction (in vitro or in situ) and exercise increase glucose uptake into skeletal muscle. However, the contraction/exercise pathway of glucose uptake in skeletal muscle is an independent pathway to that of insulin. Indeed, skeletal muscle glucose uptake is normal during exercise in those who suffer from insulin resistance and diabetes. Thus, the pathway of contraction-mediated glucose uptake into skeletal muscle provides an attractive potential target for pharmaceutical treatment and prevention of such conditions, especially as skeletal muscle is the major site of impaired glucose disposal in insulin resistance. The mechanisms regulating skeletal muscle glucose uptake during contraction have not been fully elucidated. Potential regulators include Ca2+ (via CaMK's and/or CaMKK), AMPK, ROS, and NO signaling, with some redundancy likely to be evident within the system. In this review, we attempt to briefly synthesize current evidence regarding the potential mechanisms involved in regulating skeletal muscle glucose uptake during contraction, focusing on ROS and NO signaling. While reading this review, it will become clear that this is an evolving field of research and that much more work is required to elucidate the mechanism(s) regulating skeletal muscle glucose uptake during contraction. © 2009 IUBMB IUBMB Life 61(5): 479,484, 2009 [source]


Frontal cortical afferents facilitate striatal nitric oxide transmission in vivo via a NMDA receptor and neuronal NOS-dependent mechanism

JOURNAL OF NEUROCHEMISTRY, Issue 3 2007
Stephen Sammut
Abstract Striatal nitric oxide (NO) signaling plays a critical role in modulating neural processing and motor behavior. Nitrergic interneurons receive synaptic inputs from corticostriatal neurons and are activated via ionotropic glutamate receptor stimulation. However, the afferent regulation of NO signaling is poorly characterized. The role of frontal cortical afferents in regulating NO transmission was assessed in anesthetized rats using amperometric microsensor measurements of NO efflux and local field potential recordings. Low frequency (3 Hz) electrical stimulation of the ipsilateral cortex did not consistently evoke detectable changes in striatal NO efflux. In contrast, train stimulation (30 Hz) of frontal cortical afferents facilitated NO efflux in a stimulus intensity-dependent manner. Nitric oxide efflux evoked by train stimulation was transient, reproducible over time, and attenuated by systemic administration of either the NMDA receptor antagonist MK-801 or the neuronal NO synthase inhibitors 7-nitroindazole and NG -propyl- l -arginine. The interaction between NO efflux evoked via train stimulation and local striatal neuron activity was assessed using dual microsensor and local field potential recordings carried out concurrently in the contralateral and ipsilateral striatum, respectively. Systemic administration of the non-specific NO synthase inhibitor methylene blue attenuated both evoked NO efflux and the peak oscillation frequency (within the delta band) of local field potentials recorded immediately after train stimulation. Taken together, these observations indicate that feed-forward activation of neuronal NO signaling by phasic activation of frontal cortical afferents facilitates the synchronization of glutamate driven oscillations in striatal neurons. Thus, NO signaling may act to amplify coherent corticostriatal transmission and synchronize striatal output. [source]


von Willebrand factor activates endothelial nitric oxide synthase in blood platelets by a glycoprotein Ib-dependent mechanism

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006
R. RIBA
Summary.,Background: The molecular regulation of endothelial nitric oxide synthase (eNOS) in blood platelets and the signalling events induced by platelet-derived NO are poorly defined. In particular, the ability of von Willebrand factor (VWF) to stimulate cyclic guanosine monophosphate (cGMP) formation in platelets has produced conflicting data. Objectives: To determine the mechanisms leading to eNOS activation and clarify the downstream signaling pathways activated by platelet-derived NO in response to VWF. Methods: We used three independent markers of NO signaling, [3H] l -citrulline production, cGMP accrual and immunoblotting of vasodilator,stimulated phosphoprotein (VASP) to examine the NO signaling cascade in response to VWF. Results: VWF increased NO synthesis and bioavailability, as evidenced by increased [3H] l -citrulline production and cGMP accrual, respectively. VWF-induced eNOS activation was GPIb-IX-dependent and independent of integrin ,IIb,3. cGMP formation in response to VWF required Ca2+ mobilization, Src family kinases, phosphatidylinositol 3-kinase and phospholipase C, but not protein kinase C. This suggests that a cross-talk between the signaling mechanisms regulates platelet activation and NO synthesis. VWF-induced cGMP accrual was completely blocked by apyrase and indomethacin, demonstrating an essential role for platelet-derived ADP and thromboxane A2 (TxA2). Elevated cGMP levels led to increased VASP phosphorylation at serine239 that was both protein kinase G (PKG)- and protein kinase A (PKA)-dependent. Conclusions: We demonstrate that VWF activates eNOS through a specific Ca2+ -dependent GPIb receptor-signaling cascade that relies on the generation of platelet-derived ADP and TxA2. Furthermore, we provide the first evidence to suggest that platelet derived-NO/cGMP activates PKA in addition to PKG. [source]


Three-dimensional distribution of no sources in a primary mechanosensory integration center in the locust and its implications for volume signaling

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010
Daniel Münch
Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source]


Three-dimensional distribution of NO sources in a primary mechanosensory integration center in the locust and its implications for volume signaling

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010
Daniel Münch
Abstract Nitric oxide (NO) is an evolutionarily conserved mediator of neural plasticity. Because NO is highly diffusible, signals from multiple sources might combine in space and time to affect the same target. Whether such cooperative effects occur will depend on the effective signaling range and on the distances of NO sources to one another and to their targets. These anatomical parameters have been quantified in only few systems. We analyzed the 3D architecture of NO synthase (NOS) expression in a sensory neuropil, the ventral association center (VAC) of the locust. High-resolution confocal microscopy revealed NOS immunoreactive fiber boutons in submicrometer proximity to both the axon terminals of sensory neurons and their postsynaptic target, interneuron A4I1. Pharmacological manipulation of NO signaling affected the response of A4I1 to individual wind-puff stimuli and the response decrement during repetitive stimulation. Mapping NOS immunoreactivity in defined volumes around dendrites of A4I1 revealed NOS-positive fiber boutons within 5 ,m of nearly every surface point. The mean distances between neighboring NOS-boutons and between any point within the VAC and its nearest NOS-bouton were likewise about 5 ,m. For an NO signal to convey the identity of its source, the effective signaling range would therefore have to be less than 5 ,m, and shorter still when multiple boutons release NO simultaneously. The architecture is therefore well suited to support the cooperative generation of volume signals by interaction between the signals from multiple active boutons. J. Comp. Neurol. 518:2903,2916, 2010. © 2010 Wiley-Liss, Inc. [source]


Erectile Function in Two-Kidney, One-Clip Hypertensive Rats is Maintained by a Potential Increase in Nitric Oxide Production

THE JOURNAL OF SEXUAL MEDICINE, Issue S3 2009
A. Elizabeth Linder PhD
ABSTRACT Introduction., Hypertension is closely associated with erectile dysfunction (ED) as it has been observed in many experimental models of hypertension. Additionally, epidemiological studies show that approximately a third of hypertensive patients have ED. Aim., To test the hypothesis that the two-kidney, one-clip (2K-1C) rat model of hypertension displays normal erectile function due to increased nitric oxide (NO) production in the penis. Methods., Ganglionic-induced increase in intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was used as an index of erectile function in 2K-1C and in normotensive sham-operated (SHAM) anesthetized rats. Cavernosal strips from hypertensive and normotensive rats were used for isometric tension measurement. The contraction induced by alpha-adrenergic agonist phenylephrine and the relaxation induced by the NO donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the NO synthase inhibitor N, -nitro-L-arginine (L-NNA). Results., Changes in ICP/MAP induced by ganglionic stimulation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were similar in cavernosal strips from both groups. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM. Conclusions., These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is maintained in spite of the increased Rho-kinase activity by increased NO signaling. Linder AE, Dorrance AM, Mills TM, Webb RC, and Leite R. Erectile function in two-kidney, one-clip hypertensive rats is maintained by a potential increase in nitric oxide production. J Sex Med 2009;6(suppl 3):279,285. [source]


Putative Role of Carbon Monoxide Signaling Pathway in Penile Erectile Function

THE JOURNAL OF SEXUAL MEDICINE, Issue 1 2009
Mohamed T. Abdel Aziz MD
ABSTRACT Introduction., Erectile response depends on nitric oxide (NO) generated by NO synthase (NOS) enzyme of the nerves and vascular endothelium in the cavernous tissue. NO activates soluble guanylate cyclase (sGC), leading to the production of cyclic guanosine monophosphate (cGMP). cGMP activates cGMP-dependent protein kinase that activates Ca2+/ATPase pump that activates Ca2+/K efflux pump extruding Ca2+ across the plasma membrane with consequent smooth muscle cell relaxation. A role similar to that of NOS/NO signaling has been postulated for carbon monoxide (CO) produced in mammals from heme catabolism by heme oxygenase (HO) enzyme. Aim., To assess CO signaling pathway for erectile function by reviewing published studies. Methods., A systematic review of published studies on this affair based on Pubmed and Medical Subject Heading databases, with search for all concerned articles. Main Outcome Measures., Documentation of positive as well as negative criteria of CO/HO signaling focused on penile tissue. Results., The concept that HO-derived CO could play a role in mediating erectile function acting in synergism with, or as a potentiator for, NOS/NO signaling pathway is gaining momentum. CO/HO signaling pathway has been shown to partially mediate the actions of oral phosphodiesterase type 5 inhibitors. In addition, it was shown that the use of CO releasing molecules potentiated cavernous cGMP levels. However, increased CO production or release was reported to be associated, in some studies, with vasoconstriction. Conclusion., This review sheds a light on the significance of cavernous tissue CO signaling pathway that may pave the way for creation of therapeutic modalities based on this pathway. Abdel Aziz MT, Mostafa T, Atta H, Wassef MA, Fouad HH, Rashed LA, and Sabry D. Putative role of carbon monoxide signaling pathway in penile erectile function. J Sex Med 2009;6:49,60. [source]