The Endothelium-Dependent Nitric Oxide–cGMP Pathway

Mónica, Fabíola Z.; Bian, Ka; Murad, Ferid

doi:10.1016/bs.apha.2016.05.001

Cited by 90 publications

(59 citation statements)

References 102 publications

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“…Secondly, the overexpression of the glutamatergic system can lead to the release of a large amount of NO, which can induce hippocampal neuronal damage and death and is suppressed to restore gastric motility [41]. irdly, studies have indicated that the NO-cGMP pathway plays a critical role in smooth muscle relaxation, so suppressing this pathway may promote gastric smooth muscle contraction [42]. erefore, we speculate that there may be complex mechanisms underlying the glutamatergic system in the central nervous system to regulate gastric motility, and these mechanisms remain to be explored in future experiments.…”

Section: Discussionmentioning

confidence: 99%

Acupuncture at Gastric Back‐Shu and Front‐Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus

Wang

Liu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Acupuncture strongly alleviates gastrointestinal symptoms and especially promotes gastrointestinal motility. However, the mechanism underlying these processes is poorly understood. is study was designed to examine the effect of electroacupuncture (EA) at gastric back-shu (BL21) and front-mu (RN12) acupoints on gastric motility in functional dyspepsia (FD) rats and to investigate the mechanisms of its effects on the glutamatergic system in the hippocampus. We found that EA at RN12 or BL21 enhanced gastric motility in FD rats, whereas EA at the combination of RN12 and BL21 showed an additional effect. Microdialysis combined with HPLC showed that EA reduced the glutamate content in the hippocampus, and the NMDAR-NO-cGMP signalling pathway was downregulated, as determined by Western blot assays, in FD rats. In addition, we found that decreased gastric motility was significantly restored by the hippocampal infusion of an NMDAR, nNOS, or sGC antagonist. Interestingly, EA had no further effects on gastric motility in the presence of these antagonists in FD rats. Taken together, these results suggest that the hippocampal glutamatergic system is involved in the regulation of gastric motility by EA at RN12 and BL21.

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Section: Discussionmentioning

confidence: 99%

Acupuncture at Gastric Back‐Shu and Front‐Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus

Wang

Liu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…cGMP production by guanylate cyclase is the major signal transduction mechanism of NO. NO can diffuse from where it is synthesized into surrounding cells, where it will activate soluble guanylate cyclase to produce cGMP . In turn, cGMP activates cGMP‐dependent kinases in the target tissue that regulate diverse activities to exert physiological functions, such as regulation of vascular homeostasis and facilitation of synaptic plasticity, by modulating intracellular calcium levels .…”

Section: Cross‐talk Between Ros and Rnsmentioning

confidence: 99%

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

Huang

2019

Acta Physiologica

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Oxidative stress is recognized as free radical dyshomeostasis, which has damaging effects on proteins, lipids and DNA. However, during cell differentiation and proliferation and other normal physiological processes, free radicals play a pivotal role in message transmission and are considered important messengers. Organisms maintain free radical homeostasis through a sophisticated regulatory system in which these "2faced" molecules play appropriate roles under physiological and pathological conditions. Reactive oxygen species (ROS), including a large number of free radicals, act as redox signalling molecules in essential cellular signalling pathways, including cell differentiation and proliferation. However, excessive ROS levels can induce oxidative stress, which is an important risk factor for diabetes, cancer and cardiovascular disease. An overall comprehensive understanding of ROS is beneficial for understanding the pathogenesis of certain diseases and finding new therapeutic treatments.This review primarily focuses on ROS cellular localization, sources, chemistry and molecular targets to determine how to distinguish between the roles of ROS as messengers and in oxidative stress. K E Y W O R D Shomeostasis, oxidative stress, reactive oxygen, redox signalling, signalling pathways 2 of 16 | HUANG ANd LI for the development of new therapeutic strategies for cancer and cardiovascular disease. | SOURCES AND PHYSICOCHEMICAL PROPERTIES OF ROS | ROS sourcessecond messengers, what are the corresponding acceptors for these special ROS? To better recognize ROS, a new tool that can monitor changes in ROS levels and position in real time must be developed. Determining how to utilize the characteristics of ROS to treat diseases, such as cardiovascular disease, diabetes, autoimmune diseases, cancer and Alzheimer's diseases, is worth further exploration.

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“…NO is a free radical signaling gas produced by the NO synthases (NOS) during the conversion of arginine to citrulline. 27 Endothelial-derived NO, produced by endothelial NOS (eNOS), plays a pivotal role in vascular homeostasis, 28 diffusing across the endothelial cell membrane into the adjacent smooth muscle and binding to the ferrous (Fe 2þ ) heme of soluble guanylate cyclase (sGC). Activated sGC converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP), a second messenger that activates cGMP-dependent protein kinases (PKG) to promote a cascade of effects, resulting in calcium removal from smooth muscle cells, in turn relaxing blood vessels and increasing blood flow via vasodilation.…”

Section: Evidence For the Downregulation Of No-cgmp-dependent Signalimentioning

confidence: 99%

cGMP modulation therapeutics for sickle cell disease

Conran

Torres

2019

Exp Biol Med (Maywood)

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Sickle cell disease (SCD) is an inherited disease caused by the production of abnormal hemoglobin (Hb) S, whose deoxygenation-induced polymerization results in red blood cell (RBC) sickling and numerous pathophysiological consequences. SCD affects approximately 300,000 newborns worldwide each year and is associated with acute and chronic complications, including frequent painful vaso-occlusive episodes that often require hospitalization. Chronic intravascular hemolysis in SCD significantly reduces vascular nitric oxide (NO) bioavailability, consequently decreasing intracellular signaling via cyclic guanosine monophosphate (cGMP), in turn diminishing vasodilation and contributing to the inflammatory mechanisms that trigger vaso-occlusive processes. Oxidative stress may further reduce NO bioavailability in SCD and can oxidize the intracellular enzyme target of NO, soluble guanylate cyclase (sGC), rendering it inactive. Increasing intracellular cGMP-dependent signaling constitutes an important pharmacological therapeutic approach for SCD with a view to augmenting vasodilation, and reducing inflammatory mechanisms, as well as for increasing the production of anti-polymerizing fetal Hb in erythroid cells. Pharmacological agents under pre-clinical and clinical investigation for SCD include NO-based therapeutics to augment NO bioavailability, as well as heme-dependent sGC stimulators and heme-independent sGC activators that directly stimulate native and oxidized sGC, respectively, therefore bypassing the need for vascular NO delivery. Additionally, the phosphodiesterases (PDEs) that degrade intracellular cyclic nucleotides with specific cellular distributions are attractive drug targets for SCD; PDE9 is highly expressed in hematopoietic cells, making the use of PDE9 inhibitors, originally developed for use in neurological diseases, a potential approach that could rapidly amplify intracellular cGMP concentrations in a relatively tissue-specific manner. Impact statement Sickle cell disease (SCD) is one of the most common inherited diseases and is associated with a reduced life expectancy and acute and chronic complications, including frequent painful vaso-occlusive episodes that often require hospitalization. At present, treatment of SCD is limited to hematopoietic stem cell transplant, transfusion, and limited options for pharmacotherapy, based principally on hydroxyurea therapy. This review highlights the importance of intracellular cGMP-dependent signaling pathways in SCD pathophysiology; modulation of these pathways with soluble guanylate cyclase (sGC) stimulators or phosphodiesterase (PDE) inhibitors could potentially provide vasorelaxation and anti-inflammatory effects, as well as elevate levels of anti-sickling fetal hemoglobin.

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The Endothelium-Dependent Nitric Oxide–cGMP Pathway

Cited by 90 publications

References 102 publications

Acupuncture at Gastric Back‐Shu and Front‐Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus

Acupuncture at Gastric Back‐Shu and Front‐Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

cGMP modulation therapeutics for sickle cell disease

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