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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-Nitrosoglutathione, a possible intermediate in the pharmacological mechanisms of many vasodilators, undergoes hemolysis at pH 7.4 and 37 degrees C to give oxidized glutathione and nitric oxide with a second-order rate constant of approximately 3 x 10(-4) M-1sec-1. At the dosages normally employed, this reaction is, therefore, too slow to be an obligatory step in the pharmacological mechanisms of those, usually, fast-acting drugs. Transfers of the nitroso moiety to another thiol or to certain hemoproteins are, however, both much faster and could be involved in those pharmacological mechanisms. Intravenously administered S-nitrosoglutathione reduced the blood pressure of anesthesized dogs and monkeys to the same extent and with essentially the same rapid onset and dissipation as sodium nitroprusside, which is the fastest-acting of those vasodilators.
Biochem Mol Biol Int 1993 Aug
PMID:Transnitrosation as a predominant mechanism in the hypotensive effect of S-nitrosoglutathione. 810 71

Cyclic adenosine diphosphate-ribose, an endogenous metabolite of nicotinamide adenine dinucleotide was first characterized as a potent Ca2+ mobilizing agent in sea urchin eggs. Mounting evidence points to it being an endogenous activator of Ca(2+)-induced Ca2+ release by non-skeletal muscle ryanodine receptors in several invertebrate and mammalian cell types. Cyclic adenosine diphosphate-ribose is synthesized by adenosine diphosphate-ribosyl cyclases, which have been found to be widespread enzymes. Recent data suggests that cyclic adenosine diphosphate-ribose may function as a second messenger in sea urchin eggs at fertilization and in stimulus secretion coupling in pancreatic beta-cells. A second messenger role for cyclic adenosine diphosphate-ribose requires that its intracellular levels be under the control of extracellular stimuli. Another second messenger, cGMP, stimulates the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide adenine dinucleotide by activating the adenosine diphosphate-ribosyl cyclase pathway in sera urchin eggs and egg homogenates, suggesting that cyclic adenosine diphosphate-ribose may be an intracellular messenger for cell surface receptors or nitric oxide, which activate cGMP-producing guanylate cyclases. Cyclic adenosine diphosphate-ribose may have a similar role to inositol trisphosphate in controlling intracellular calcium signalling with these two calcium-mobilizing second messengers activating ryanodine receptors and inositol trisphosphate receptors respectively.
Mol Cell Endocrinol 1994 Jan
PMID:Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling. 814 21

Crystals of cytochrome P450nor (P450nor), nitric oxide reductase from Fusarium oxysporum, were obtained by means of the hanging-drop vapour diffusion technique in the presence of 1.88 M ammonium sulphate (pH 7.2). They belong to the monoclinic space group P2(1), with unit cell dimensions of a = 74.7 A, b = 86.7 A, c = 62.0 A and beta = 97 degrees. There are two molecules of P450nor in the asymmetric unit. The crystal diffracted to beyond 2.5 A resolution and is suitable for X-ray crystallographic study.
J Mol Biol 1994 May 27
PMID:Crystallization and preliminary X-ray diffraction studies of nitric oxide reductase cytochrome P450nor from Fusarium oxysporum. 819 45

The endothelial cells inhibit the tone of the underlying vascular smooth muscle by releasing endothelium-derived relaxing factors (EDRF). The existence of at least two such factors, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), has been demonstrated. EDHF is an as yet unidentified substance that hyperpolarizes vascular smooth muscle cells and causes their relaxation. The contribution of endothelium-dependent hyperpolarization varies along the vascular tree. Particularly in smaller blood vessels, EDHF acts on vascular smooth muscle in cooperation with nitric oxide. Basal release of EDHF is not likely to occur, at least in vitro. The production and/or release of EDHF is regulated by the cytosolic concentration of Ca2+ ions, derived both from the extracellular space and intracellular stores. Calmodulin may be involved in its production and/or release. EDHF hyperpolarizes the vascular smooth muscle by opening K+ channels. The hyperpolarization closes voltage-dependent Ca2+ channels and, as a consequence, EDHF relaxes blood vessels. In the absence of chemical identification of EDHF, it is difficult to assess its contribution to endothelium-dependent relaxations in vivo.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. 838 Feb 48

Nitric oxide (NO) is an intercellular mediator produced within the cerebellum and other central nervous system sites. Results from the present study suggest a novel role for this gaseous second messenger in mediating the stimulatory actions of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) on turnover of phosphatidylinositol (PI) in the neonatal cerebellum. Activation of the NMDA receptor stimulates PI turnover in developing cerebellum when these neurons are in a depolarized state, but the mechanism underlying this effect is unknown. We measured changes in PI hydrolysis induced by NMDA in the presence of baclofen, which is known to depolarize neurons by activating presynaptic inhibitory gamma-aminobutyric acidB autoreceptors. NMDA increased PI hydrolysis by 80% in the presence of 1 microM baclofen. This modulatory action of NMDA was prevented by two competitive inhibitors of NO synthase, L-NG-monomethylarginine and L-N omega-nitroarginine, as well as by hemoglobin, which binds NO. Inhibition of NMDA-induced PI hydrolysis by L-NG-monomethylarginine was reversed by prior administration of L-arginine (200 microM), the physiological substrate of NO synthase. Arginine (500 microM) alone was also able to increase PI hydrolysis significantly. Superoxide dismutase, which prolongs the half-life of NO, also significantly increased the ability of NMDA to stimulate PI hydrolysis. However, NO-induced activation of the cGMP pathway did not appear to be responsible for the NMDA-induced increase in PI hydrolysis, because addition of 8-bromo-cGMP decreased this parameter, and methylene blue, which blocks guanylate cyclase activity, did not inhibit the PI hydrolysis evoked by NMDA receptor activation. These results suggest that NMDA receptor activation acts to release NO, which then acts through a novel pathway to enhance the hydrolysis of PI in the developing rat cerebellum. This novel role for NO in mediating the stimulatory actions of NMDA on PI hydrolysis may be important for developmental processes in the central nervous system.
Mol Pharmacol 1993 Jan
PMID:Novel action of nitric oxide as mediator of N-methyl-D-aspartate-induced phosphatidylinositol hydrolysis in neonatal rat cerebellum. 838 Aug 82

The effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] on ionic current responses produced by ionotropic glutamate and gamma-aminobutyric acid (GABA)A receptor activation in the nucleus of the tractus solitarius (NTS) were examined. Recordings were made in the dorsomedial subdivision of the NTS adjacent to the area postrema in transverse brainstem slices of the rat. (1S,3R)-ACPD produced a small inward current (IACPD) associated with a decrease in conductance in approximately 50% of recordings. Monosynaptic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the region of the tractus solitarius in the presence of D-amino-5-phosphonopentanoic acid and bicuculline were reversibly reduced by (1S,3R)-ACPD in > 90% of cells. The inward current evoked by pressure application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (IAMPA) was potentiated in the presence of (1S,3R)-ACPD, whereas the outward current evoked by the GABAA receptor agonist muscimol (IMUSC) was inhibited. We have previously demonstrated that these effects may involve the activation of soluble guanylate cyclase. The diffusible second messengers nitric oxide and carbon monoxide are known to activate soluble guanylate cyclase. The nitric oxide synthase inhibitor L-omega-nitroarginine failed to inhibit responses to (1S,3R)-ACPD. The selective heme oxygenase inhibitor Zn-protoporphyrin-IX, which would be expected to block the production of carbon monoxide, antagonized the effects of (1S,3R)-ACPD on EPSCs, IAMPA, and IMUSC. However, IACPD was not blocked. A relatively inactive metalloprotoporphyrin, Cu-protoporphyrin-IX was ineffective. A cell-permeant form of cGMP, 8-Br-cGMP inhibited EPSCs, IAMPA, and IMUSC in the presence of Zn-protoporphyrin-IX but did not induce an inward current. These results further support the hypothesis that multiple metabotropic glutamate receptors exist in the NTS, and they suggest that one of these may be coupled to the activation of a soluble guanylate cyclase via the liberation of an easily diffusible second messenger such as carbon monoxide.
Mol Pharmacol 1993 Jun
PMID:Zinc protoporphyrin-IX blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarii. 839 Nov 21

The amino acid sequence of mouse brain beta spectrin (beta fodrin), deduced from the nucleotide sequence of complementary DNA clones, reveals that this non-erythroid beta spectrin comprises 2363 residues, with a molecular weight of 274,449 Da. Brain beta spectrin contains three structural domains and we suggest the position of several functional domains including f-actin, synapsin I, ankyrin and spectrin self association sites. Analysis of deduced amino acid sequences indicated striking homology and similar structural characteristics of brain beta spectrin repeats beta 11 and beta 12 to globins. In vitro analysis has demonstrated that heme is capable of specific attachment to brain spectrin, suggesting possible new functions in electron transfer, oxygen binding, nitric oxide binding or heme scavenging.
Brain Res Mol Brain Res 1993 Apr
PMID:The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences. 847 93

Lipopolysaccharide (LPS) treatment results in widespread expression of the inducible isoform of nitric oxide (NO) synthase (iNOS). Although there is evidence for the expression of iNOS in heart tissue, regulation of myocardial iNOS expression is not known. To determine the time course and degree of iNOS induction in the adult heart, we examined iNOS mRNA expression and enzyme activity in (1) rat left ventricular tissue after LPS treatment in vivo, and (2) cultured, long-term rat cardiac myocytes maintained in serum and exposed to interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma, and/or LPS. iNOS mRNA was detected by Northern blot analysis and in situ hybridization. iNOS enzyme activity was measured in extracts of whole heart, and nitrate and nitrite (the stable end-products of NO) accumulation was quantified in cardiomyocyte culture media. iNOS mRNA was not detected in untreated hearts or cultured myocytes but was apparent within 3 h in both hearts obtained from LPS-treated animals and in cytokine-treated myocytes. In whole heart, iNOS mRNA expression peaked by 6 h after LPS and declined by 12 and 24 h. In situ hybridization demonstrated perinuclear localization of iNOS mRNA in both cardiac vascular smooth muscle and myocytes with maximal expression at 6 h after LPS injection. In cardiac myocytes, iNOS expression was maximal at 12 to 24 h, persisted through 48 h, and was partially inhibited by dexamethasone. Interferon-gamma was the most potent single cytokine with regards to myocyte iNOS induction. Nitric oxide release in cytokine-stimulated cardiac myocytes was largely in the form of nitrate and was associated with increased glucose uptake and lactate release; the former finding indicates that NO interacts with myocardial heme proteins and/or oxyradicals, while the latter suggests inhibition of oxidative metabolism. Although non-myocardial cells may significantly contribute to iNOS expression in whole heart tissue, significant iNOS expression and NO production also take place within the myocyte. Induced NO production may regulate myocardial perfusion and impair myocardial function and metabolism.
J Mol Cell Cardiol 1995 Sep
PMID:Characterization of inducible nitric oxide synthase expression in endotoxemic rat cardiac myocytes in vivo and following cytokine exposure in vitro. 852 61

Cisplatin is a prominent member of the effective broad spectrum antitumor drugs. The clinical usage of cisplatin is, however, restricted due to some adverse side effects including renal toxicity. The present study demonstrates the protective effect of a Zinc-chelate of histidine, [Zn-Hist], against cisplatin induced nephrotoxicity and gastrointestinal toxicity as shown by decreases in BUN, creatinine and lower incidence of diarrhoea. The observed inhibition in cisplatin induced renal and hepatic lipid peroxidation by [Zn-Hist] pretreatment, suggests an importance for Zn in stabilisation of membrane integrity probably through the displacement of the redox-active metals that may be responsible for inducing peroxidative damage at target sites. The findings also suggest that cisplatin may play biochemical role in arginine-metabolism including nitric oxide (NO) production.
Biochem Mol Biol Int 1995 Jul
PMID:Reduction of cis-platinum induced nephrotoxicity by zinc histidine complex : the possible implication of nitric oxide. 852 48

Effects of aminoethylisothiuronium bromide (AET), known as radioprotector, on human platelet soluble guanylate cyclase and on ADP-induced human platelets aggregation were studied. It was shown that AET - in Tris buffer and at certain pH values - is converted, via transguanidine rearrangement, to mercaptoethylguanidine. The latter contains in its molecule both the guanidine and SH groups which act as donor and acceptor of nitric oxide (NO), respectively. It was demonstrated that AET, after its rearrangement to mercaptoethylguanidine, is able to activate human platelet soluble guanylate cyclase, as well as to inhibit ADP-induced human stimulatory effect of AET is dependent on the effectiveness of its transguanidine rearrangement to mercaptoethylguanidine. The molecular mechanism of the hypotensive by - effect of AET is proposed.
Biochem Mol Biol Int 1995 Jul
PMID:Guanidine thiol--a new activator of soluble guanylate cyclase with antihypertensive and antiaggregatory properties. 852 55


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