Methylene Blue, a Soluble Guanylyl Cyclase Inhibitor, Reduces the Sevoflurane Minimum Alveolar Anesthetic Concentration and Decreases the Brain Cyclic Guanosine Monophosphate Content in Rats

1999 ◽  
Vol 89 (2) ◽  
pp. 484-489 ◽  
Author(s):  
Eiji Masaki ◽  
Ichiro Kondo
Keyword(s):  
Methylene Blue ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Anesthetic Concentration ◽  
The Brain

scholarly journals Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

2020 ◽  
Author(s):  
Thomas J Pirtle ◽  
Richard A Satterlie
Keyword(s):  
Nitric Oxide ◽  
Central Pattern Generator ◽  
Guanylyl Cyclase ◽  
Signal Transduction Pathway ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Pattern Generator ◽  
Guanosine Monophosphate ◽  
Cellular Changes ◽  
Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

scholarly journals cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

2019 ◽  
Vol 393 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Andreas Friebe ◽  
Peter Sandner ◽  
Achim Schmidtko
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cell Types ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Therapeutic Implications ◽  
Cellular Effects ◽  
Recent Developments ◽  
And Function ◽  
Messenger Molecule

AbstractCyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC- and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the “9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications” held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

Exogenous Irritant-Induced Airway Hyperreactivity and Inhibition of Soluble Guanylyl Cyclase

2008 ◽  
Vol 10 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Martina Antošová ◽  
Anna Strapková ◽  
Tomáš Turčan
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Respiratory System ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Airway Hyperreactivity ◽  
Guanosine Monophosphate ◽  
Airway Reactivity ◽  
Subsequent Increase ◽  
Animal Group

The majority of nitric oxide (NO) effects in the respiratory system are caused by stimulation of soluble guanylyl cyclase (sGC) with subsequent increase of cyclic guanosine monophosphate (cGMP) production. The importance of this mechanism of NO action in airway hyperreactivity (AHR) pathogenesis is unknown. Therefore, the aim of our experiment was to examine the changes of airway reactivity enhanced by toluene vapor exposure in the presence or inhibition of sGC activity in guinea pigs. Animals were treated with a nonspecific sGC inhibitor, methylene blue, in a dose of 50 or 100 mg/kg body weight, administered by intraperitoneal injection 30 min before or after exposure to toluene vapors. The toluene exposure lasted 2 hr in each of 3 consecutive days under in vivo conditions. Thereafter, the tracheal and lung tissue smooth muscle response to cumulative doses of mediators (histamine or acetylcholine) was recorded under in vitro conditions. The exposure to toluene vapors significantly increased the airway reactivity to both mediators in comparison with the healthy animal group. The administration of methylene blue decreased the amplitude of airway smooth muscle contraction in toluene-induced hyperreactivity. The decreases were dependent on the inhibitor doses, on a regimen of administration (before or after toluene inhalation), the level of the respiratory system (trachea, lung), and the bronchoconstrictor mediators. Our results suggest that the interaction between NO and sGC may be important for airway reactivity changes, but other mechanisms of NO action are important in AHR pathogenesis, too.

scholarly journals Genetics of guanylyl cyclase pathways in the cochlea and their influence on hearing

2018 ◽  
Vol 50 (9) ◽  
pp. 780-806 ◽  
Author(s):  
Janet L. Fitzakerley ◽  
George J. Trachte
Keyword(s):  
Hearing Loss ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cochlear Function ◽  
Medical Interventions ◽  
Downstream Effectors ◽  
Harmful Effects

Although hearing loss is the most common sensory deficit in Western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function and discuss the known functions of downstream effectors of cGMP in sound processing. The nitric oxide-stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide-stimulated particulate GCs (pGCs) will be more extensively covered because they have been studied most thoroughly. The cochlear GC systems are attractive targets for medical interventions that improve hearing while simultaneously representing an under investigated source of sensorineural hearing loss.

Soluble guanylyl cyclase is the only enzyme responsible for cyclic guanosine monophosphate synthesis in human platelets

2013 ◽  
Vol 109 (05) ◽  
pp. 973-975 ◽  
Author(s):  
Hariharan Subramanian ◽  
Natalia Rukoyatkina ◽  
Sabine Herterich ◽  
Ulrich Walter ◽  
Stepan Gambaryan
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Human Platelets ◽  
Guanosine Monophosphate

Abstract 2494: Beneficial Actions of Co-Targeting Particulate and Soluble Guanylate Cyclase Dependent cGMP Pools in Experimental Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Guido Boerrigter ◽  
Lisa C Costello-Boerrigter ◽  
Harald Lapp ◽  
Johannes-Peter Stasch ◽  
John C Burnett
Keyword(s):  
Heart Failure ◽  
Guanylyl Cyclase ◽  
Sodium Excretion ◽  
Soluble Guanylate Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Urinary Sodium Excretion ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Right Atrial ◽  
Cardiac Unloading

Background: B-type natriuretic peptide (BNP) signals via particulate guanylyl cyclase (pGC) and cyclic guanosine monophosphate (cGMP). In heart failure (HF), BNP reduces cardiac filling pressures and in selected patients augments sodium excretion and glomerular filtration rate (GFR). Studies have established that pGC and soluble guanylyl cyclase (sGC), the main target of nitric oxide (NO), can be compartmentalized with both enzymes affecting distinct intracellular cGMP pools, resulting in different biological actions. Importantly, sGC may be oxidized in disease states like HF making it unresponsive to NO and nitrovasodilators. BAY 58 –2667 (BAY) is a novel NO and heme independent sGC activator that preferentially stimulates oxidized sGC. We hypothesized that adding direct sGC stimulation with BAY to pGC activation with BNP in HF would enhance vasodilation and cardiac unloading without attenuating the distinct renal actions of BNP. Methods: Severe HF was induced by tachypacing in 13 dogs. On day 11, cardiorenal function was assessed in an acute study under anesthesia at baseline and with intravenous BNP (50 ng/kg/min) alone or in combination with BAY (0.3 ug/kg/min). Results: BNP significantly increased urine flow (UV), urinary sodium excretion (UNaV), GFR, renal blood flow (RBF) and systemic vascular resistance (SVR) and decreased cardiac output (CO), mean arterial pressure (MAP), right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP). Despite a greater decrease in MAP compared to BNP, BAY+BNP resulted in similar increases in UNaV, UV and GFR. Dual pGC and sGC stimulation resulted in greater decreases in SVR, RAP and PCWP together with an augmentation of CO compared to BNP alone. Conclusion: Particulate GC activation with BNP in experimental HF enhances renal function and leads to renal but not systemic vasodilation. Addition of the sGC stimulator BAY provides systemic vasodilation, greater cardiac unloading, and augmented CO. Despite a larger decrease in MAP, additional sGC stimulation does not impair the renal actions observed with pGC stimulation alone. These findings support coactivation of sGC with BAY and pGC with BNP as a novel and beneficial therapeutic strategy in HF to optimize activation of distinct GC enzymes and cGMP.

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