Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Segments of endothelium-denuded pulmonary arterial and aortic rings and strips of corpus cavernosum from rabbits were superfused with Krebs solution alone and then Krebs medium containing 0.1-0.5 mM N omega-Nitro-L-Arginine. Photorelaxation in response to ultraviolet light (366 nm) was significantly enhanced by 50 microM methylene blue in all preparations; 25 microM methylene blue also increased photorelaxation in corpus cavernosum and pulmonary artery. Enhanced photorelaxation was associated with increased tissue cGMP. This effect was significantly attenuated by 10 microM hemoglobin and was associated with decreased tissue cGMP but was unaffected by superoxide dismutase. We speculate that UV-generated free radicals convert the phenothiazine moiety of methylene blue to a phenyl radical which activates guanylate cyclase and thus enhances smooth muscle relaxation.
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PMID:Methylene blue enhanced photorelaxation in aorta, pulmonary artery and corpus cavernosum. 838 Dec 79

Nitric oxide (NO) is a small, gaseous, paramagnetic radical with a high affinity for interaction with ferrous hemoproteins such as soluble guanylate cyclase and hemoglobin. Interest in NO measurement increased exponentially with the discovery that NO or a related compound is the endothelium-derived relaxing factor (EDRF). In addition to being a potent endogenous vasodilator, NO has a role in inflammation, thrombosis, immunity, and neurotransmission. Measurement of NO is important as many of its effects (e.g., vasodilatation, inhibition of platelet aggregation) are similar to those of other substances produced by the endothelium, such as prostacyclin. NO is formed in small amounts in vivo and is rapidly destroyed by interaction with oxygen, making measurement difficult. A computerized search of the past five year's literature found NO measurements reported in fewer than 50 of 955 articles dealing with EDRF. Inhibitors of NO synthesis such as the arginine analogs or agents that inactivate NO, such as reduced hemoglobin, are commonly used as specific probes for NO, in vivo and in vitro; however, none of the NO inhibitors is completely specific. The most widely used assays use one of three strategies to detect NO: 1) NO is "trapped" by nitroso compounds, or reduced hemoglobin, forming a stable adduct that is detected by electron paramagnetic resonance (EPR) (detection threshold approximately 1 nmol); 2) NO oxidizes reduced hemoglobin to methemoglobin, which is detected by spectrophotometry (detection threshold approximately 1 nmol); 3) NO interacts with ozone producing light, "chemiluminescence" (detection threshold approximately 20 pmol). These assays can be performed to exclusively detect NO, or by adding acid and reducing agents to the sample, can measure NO and related oxides of nitrogen such as nitrite. Several new amperometric microelectrode assays offer the potential to measure smaller amounts of NO (10(-20) M), permitting NO measurement in intact issues and from single cells. This review describes the pharmacology and toxicology of NO and reviews the major techniques for measuring NO in biological models.
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PMID:Measurement of nitric oxide in biological models. 844 Apr 11

Nitroprusside and two newly synthesized direct-acting mutagens, N-nitroso-2-fluorenylactamide and N-nitroso-dinitroacetaminophen, were able to elicit the concentration-dependent relaxation of rat aorta. The vascular responses could be antagonized by hemoglobin that binds nitric oxide with high affinity and by methylene blue which inhibits soluble guanylate cyclase activity. We used four bases in DNA as the substrates to test the capacity to deaminate of the two compounds. Xanthine, hypoxanthine and uracil as well as some unusual bases such as 8-OH-adenine and 8-OH-guanine were found. These findings suggest that both the muscle relaxation and mutagenicity of these two compounds might be due to the release of nitric oxide in living cells.
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PMID:Relaxation of rat thoracic aorta by N-nitroso compounds and nitroprusside and their modifications of nucleic acid bases through release of nitric oxide. 845 56

Ephedrine is the preferred vasoconstrictor for the treatment of hypotension after epidural and spinal anesthesia in obstetrics because it preserves uterine perfusion better than pure alpha-adrenergic agonists. Previous studies of uterine vascular rings in vitro suggested that direct uterine vasoconstriction from ephedrine is reduced during pregnancy. This study examined the hypothesis that nitric oxide synthase (NOS) is up-regulated in uterine arteries during pregnancy, and that ephedrine stimulates NOS to release nitric oxide (NO) and diminish direct vasoconstriction. Uterine arterial vessels were obtained from 12 pregnant and 9 nonpregnant ewes, and vessel tension was monitored in vitro in response to escalating concentrations of ephedrine or metaraminol. In some experiments, vascular endothelium was mechanically removed, while in others antagonists of NO synthesis (N omega-nitro-L-arginine methyl ester [L-NAME], NO diffusion (hemoglobin [Hgb]), or guanylate cyclase (methylene blue [MB]) were included. In other experiments, solutions containing ephedrine were superfused over uterine arteries from pregnant ewes onto uterine arteries from nonpregnant ewes. Finally, NOS activity, determined by 14C-citrulline generation, was determined in uterine arteries from pregnant and nonpregnant ewes. Both ephedrine and metaraminol caused concentration-dependent constriction of uterine arterial rings from pregnant and nonpregnant animals. Pregnancy reduced maximum constriction from ephedrine more than metaraminol. Similarly, ephedrine-induced constriction was increased more than that of metaraminol in uterine arteries from pregnant animals treated to diminish the effects of nitric oxide (L-NAME, Hgb, MB, endothelium removal). Ephedrine's constriction of uterine arteries from nonpregnant animals was reduced when it was superfused over uterine arteries from pregnant animals. NOS activity was increased in uterine arteries from pregnant compared to nonpregnant animals. These studies confirm decreased direct uterine arterial vasoconstriction during pregnancy from ephedrine and support the hypothesis of increased release of an endogenous vasodilator (NO), either from the vascular endothelium or the vessel wall, as the cause for this decreased vasoconstriction.
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PMID:Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine arteries. 856 28

In order to investigate the mechanism of action by which oxytocin induces penile erection, the effect of NG-nitro-L-arginine methyl ester (NAME) and NG-monomethyl-L-arginine (NMMA), inhibitors of nitric oxide (NO) synthase, injected into the paraventricular nucleus of the hypothalamus (PVN) on the response to oxytocin injected into the PVN was studied in male rats. NAME and NMMA, but not NG-mono-methyl-D-arginine (D-NMMA), which does not inhibit NO-synthase, prevented in a dose-dependent manner the response to oxytocin. NAME was 4-5 times more potent than NMMA. NAME prevention of the oxytocin effect was not observed when NAME was given together with L-arginine but not with D-arginine. Oxytocin-induced penile erection was prevented by the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin and by methylene blue, an inhibitor of guanylate cyclase, but not reduced hemoglobin, a NO scavenger, given intracerebroventricularly (i.c.v.). In contrast, both methylene blue and hemoglobin were ineffective when injected into the PVN, unlike d(CH2)5Tyr(Me)-Orn8-vasotocin. Penile erection was induced also by sodium nitroprusside and hydroxylamine, two NO donors, injected into the PVN. Like the oxytocin effect, the NO donor response was prevented by i.c.v. d(CH2)5Tyr(Me)-Orn8-vasotocin and methylene blue, but not hemoglobin. In contrast, the three compounds were ineffective in preventing the NO donor response when injected into the PVN. The present results suggest that oxytocin induces penile erection by activating NO synthase in the PVN. NO in turn activates oxytocinergic neurons projecting to extra-hypothalamic areas that control the expression of this male sexual function by a guanosine cyclic 3':5'-monophosphate (cGMP) independent mechanism at least in the PVN.
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PMID:Oxytocin-induced penile erection. Role of nitric oxide. 871 73

The role of nitric oxide (NO) in the activity of cyclooxygenase (COX) in cultured canine tracheal epithelium was studied. Tracheal epithelium spontaneously released prostaglandin E2 (PGE2), which is a product of COX. The release of PGE2 was increased by bradykinin and was decreased by two NO synthase inhibitors: NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. That decrease was reversed in the presence of L-arginine. Chrolpromadin, but not aminoguanidine, inhibited PGE2 production, which suggests that constitutive NO synthase is involved. Two stable NO donors, sodium nitroprusside and S-nitroso-N-acetyl DL-penicillamine, also increased the production of PGE2. These effects were abolished by coincubation with hemoglobin, which binds and inactivates NO, but not by methylene blue, an inhibitor of soluble guanylate cyclase. NADPH diaphorase histochemistry of cultured tracheal cells revealed activity in the periphery of the cytoplasm. These results suggest that, in cultured canine tracheal epithelium, NO directly interacts with COX to regulate PGE2 production.
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PMID:[Regulation of cyclooxygenase activity in airway epithelium by endogenous nitric oxide]. 874 27

Nitric oxide (NO) and carbon monoxide (CO) have been identified as two diffusible signaling messengers in the brain, capable of stimulating soluble guanylate cyclase. Locus coeruleus (LC) is rich in the alpha 1 and beta 1 subunits of soluble guanylate cyclase. Therefore, the possible role of the cGMP pathway in the regulation of LC neurons was investigated with electrophysiological techniques in rat brain slices. Bath application of various NO donors or CO-containing solutions increased the firing rate of most LC neurons. This activation was reversed by the NO scavenger hemoglobin, but not by methemoglobin. Bath or intracellular application of selective activators of cGMP-dependent protein kinase also caused increases in LC cell firing rate. The actions of NO donors and kinase activators were mutually occlusive and reversed by H8, an inhibitor of the cGMP-dependent protein kinase. Hemoglobin and H8 reduced the firing rate of LC neurons, but no change was found with inhibitors or activators of the NO synthase. In intracellular and whole-cell recordings, NO effect was associated with an inward current and an increase in the input conductance (mean reversal potential = -27 mV); these effects were abolished using a low-sodium buffer. Spontaneous EPSCs of LC cells were not modified with the NO donor administration. Taken together, these data suggest that NO and CO activate noradrenergic neurons of LC via a cGMP-dependent protein kinase and a nonselective cationic channel. It also is proposed that these effects occur at the postsynaptic level and that there may be a tonic regulation of LC neuronal firing by the cGMP pathway.
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PMID:Nitric oxide and carbon monoxide activate locus coeruleus neurons through a cGMP-dependent protein kinase: involvement of a nonselective cationic channel. 877 90

In order to provide further support for a role of central nitric oxide as a mediator of penile erection and yawning, the nitric oxide donors sodium nitroprusside, hydroxylamine, isoamyl nitrite and S-nitroso-N-acetyl-penicillamine were injected into the lateral ventricles (i.c.v.) or into the paraventricular nucleus of the hypothalamus of male rats. Of the above compounds injected i.c.v., only isoamyl nitrite (10-100 micrograms) induced penile erection and yawning, while the others induced dramatic behavioral changes, such as motor hyperactivity and convulsions, that masked the above responses. Nevertheless, nitric oxide donors in doses ranging from 10 to 50 micrograms, for except S-nitroso-N-acetyl-penicillamine that was injected only at the dose of 10 micrograms and isoamyl nitrite that was not injected at all because of poor solubility, induced penile erection and yawning when injected in the paraventricular nucleus. Nitric oxide donor-induced responses were prevented by methylene blue and LY 83583, inhibitors of guanylate cyclase, the best known target of nitric oxide, given i.c.v. but not in the paraventricular nucleus. However, 8-bromo-guanosine 3':5'-cyclic monophosphate (8-Br-cGMP), a stable cGMP analog, and hemoglobin, a nitric oxide scavenger, were ineffective in inducing and preventing, respectively, penile erection and yawning when injected either i.c.v. or in the paraventricular nucleus. Nitric oxide donor-induced responses were also prevented by the nonapeptide oxytocin receptor antagonist d(CH2)5-Tyr(Me)-Orn8-vasotocin given i.c.v. but not in the paraventricular nucleus. The present results suggest that nitric oxide donors induce penile erection and yawning by activating central oxytocinergic transmission in the paraventricular nucleus of the hypothalamus via a cGMP-independent mechanism.
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PMID:Nitric oxide donors induce penile erection and yawning when injected in the central nervous system of male rats. 878 10

Carbon monoxide (CO) enhanced random migration of human neutrophils. An optimally stimulatory effect was observed with 10 microM CO. CO caused a rapid and transient increase in intracellular level of guanosine-3',5'-cyclic monophosphate (cGMP). The enhancing effect of CO on random migration was reversed to a large extent by inhibitors of cGMP accumulation, and by antagonists of cGMP-dependent protein kinase (G-kinase). These results strongly suggest that the enhancement of random migration by CO is mediated by cGMP and G-kinase. Using hemoglobin, a scavenger of CO, we could show that stimulation of soluble guanylate cyclase over an extended period of time, rather than the observed fast and transient increase in intracellular cGMP levels, is responsible for CO-activated migration. We postulate that CO, like nitric oxide (NO), acts as a biological signal in the immune system.
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PMID:Carbon monoxide enhances human neutrophil migration in a cyclic GMP-dependent way. 880 86

The non-adrenergic non-cholinergic (NANC) relaxatory response in mouse isolated whole stomach was investigated by electrical vagal stimulation (EVS) to clarify whether nitric oxide (NO) mediates vagal NANC transmission. The stomach was mounted in an organ bath, and the intragastric pressure was measured. Dual electrodes were placed on the esophagus. In the presence of atropine, propranolol and phentolamine, EVS induced a marked gastric relaxation. The response was frequency-dependent, and reproducible by repeated stimulation. The response was blocked by hexamethonium and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, and significantly depressed by methylene blue, a soluble guanylate cyclase inhibitor, but not by hemoglobin, a radical trapping agent. The inhibitory effect of L-NNA was reversed by L-arginine, a substrate for NO synthase, but not by D-arginine. Exogenous NO caused a relaxation that was inhibited by hemoglobin and methylene blue, but not by L-NNA. The electrical field stimulation also elicited a gastric relaxation that was inhibited by L-NNA and methylene blue, but not by hexamethonium and hemoglobin. These results suggest that the inhibitory NANC response to EVS in the mouse stomach is largely mediated by release of NO, and it is exclusively due to stimulation of vagal preganglionic neurons.
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PMID:Pharmacological features of non-adrenergic non-cholinergic (NANC) relaxation induced by electrical vagal stimulation in isolated mouse stomach. 884 35


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