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Query: CAS:7665-99-8 (cGMP)
 21,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An equilibrium kinetics model is proposed to described some of the enzymatic properties of the cyclic GMP-stimulated phosphodiesterase activity associated with brain clathrin coated vesicles. The model assumes the presence of pharmacologically distinct regulatory and catalytic domains in the enzyme. The model contemplates that random fashion occupancy of the regulatory site by the substrate, cyclic GMP, induces a conformational change which leads to the generation of an actived catalytic state. Therefore, cyclic GMP is a positive allosteric modulator of the coated vesicle enzyme. Experimental data revealed that occupancy or activation of the regulatory site was not essential for catalysis to occur since hydrolysis occurred after loss (200%) of the activation by cyclic GMP. This constitutes an example of non-essential substrate activation. Analysis of this PDE following activation by cGMP and after loss of the regulation, activation capacity of the enzyme allows the calculation of the various kinetic parameters inherent in the model.
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PMID:Equilibrium kinetics model for the cGMP-stimulated phosphodiesterase of brain coated vesicles. 196 77

Experiments were carried out in order to isolate and characterize the cyclic nucleotide phosphodiesterase activities in primary and low passages of cultured bovine aortic endothelial cells. The subcellular characterization of the cyclic nucleotide hydrolytic activity showed that both cAMP and cGMP hydrolytic activities were predominant in the cytosolic rather than the particulate fraction of the endothelial cell homogenate. At a low substrate concentration (0.25 microM), the major hydrolytic activity was for cAMP while at a high concentration (20 microM) it was for both cAMP and cGMP. Both cAMP and cGMP hydrolytic activities were insensitive to calmodulin. Cytosolic cyclic nucleotide phosphodiesterase activity was resolved into two distinct phosphodiesterase forms using HPLC. The first eluted form was designated cGS-PDE: it hydrolysed both cAMP and cGMP and its cAMP hydrolytic activity was markedly enhanced by the presence of cGMP. The second form was designated cAMP-PDE: it selectively hydrolysed cAMP. The cytosolic cAMP-PDE was inhibited by micromolar concentrations of cAMP-PDE inhibitors such as trequinsin, rolipram, dipyridamole or papaverine. The cGS-PDE was inhibited by micromolar concentrations of trequinsin, dipyridamole and papaverine and was insensitive to rolipram, except for the hydrolysis of cAMP which was inhibited in the micromolar range. Both the cAMP-PDE and the cGS-PDE were relatively insensitive to the selective cGMP-PDE inhibitor, zaprinast which was about 750-fold less potent on endothelial PDEs than on smooth muscle cGMP-PDE. The identification of selective and specific PDE inhibitors of the different PDE forms may allow a better understanding of the regulation and the role of cyclic nucleotides in endothelial cells.
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PMID:Characterization of cyclic nucleotide phosphodiesterases from cultured bovine aortic endothelial cells. 215 83

Incubation of intact rat fat cells with maximally effective concentrations of insulin (1 nM, 12 min) or isoprenaline (300 nM, 3 min) increased particulate cGMP- and cilostamide-inhibited, low-Km cAMP phosphodiesterase (cAMP-PDE) activity by about 50% and 100%, respectively. In 32P-labeled cells, these agents induced serine 32P-phosphorylation of a 135-kDa particulate protein and, to a variable and lesser extent, a 44-kDa protein, which were selectively immunoprecipitated by anti-cAMP-PDE, as analyzed by SDS/PAGE and autoradiography. In the absence of hormonal stimulation, little phosphorylation was detected (less than 10% of that with the hormones). The two phosphoproteins were identified as cAMP-PDE or a closely related molecule (in the case of the 44-kDa species, perhaps a proteolytic fragment) since (i) amounts of 32P in the immunoprecipitated 135-kDa protein paralleled enzyme inactivation, (ii) prior incubation of the anti-cAMP-PDE with the pure rat or bovine enzyme selectively blocked the immunoprecipitation of the phosphoproteins, (iii) 135- and 44-kDa proteins reacted with the anti-cAMP-PDE on Western immunoblots, and (iv) the two phosphoproteins copurified with cAMP-PDE activity through DEAE-Sephacel chromatography and were isolated by highly selective affinity chromatography on cilostamide-agarose. Thus, in fat cells, catecholamine- and insulin-induced activation of the cAMP-PDE may be mediated via phosphorylation by cAMP-dependent protein kinase and an insulin-activated serine protein kinase, respectively.
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PMID:Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. 215 56

Cyclic GMP-phosphodiesterase (cGMP-PDE) plays a key role in the normal functioning of retinal rod photoreceptor cells. The enzyme is composed of alpha- and beta-catalytic subunits which are inhibited by two identical gamma-subunits. A cDNA encoding the gamma-subunits (PDE gamma) from human retina has been cloned and sequenced. The 1012-bp cDNA has a coding region of 261 bp which is highly homologous to those of the PDE gamma cDNAs from bovine and mouse retinas. Comparison of the deduced amino acid sequences of the proteins from the three species indicates that PDE gamma has been very well conserved through evolution. The mRNA encoded by the cloned cDNA is 1.0 kb long, is similar in size to the corresponding mRNAs from mouse, dog and bovine retinas and is not detected in ground squirrel retina. The PDEG gene has been assigned to human chromosome 17, probably in the region q21.1.
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PMID:Isolation and characterization of cDNA encoding the gamma-subunit of cGMP phosphodiesterase in human retina. 216 80

Pretreatment of rat thymic lymphocytes with Concanavalin A induced a very early (30 min) and substantial increase (+90%) of the soluble cAMP phosphodiesterase activity. The crude cytosolic phosphodiesterase activity of rat thymocytes could reproducively be resolved by Mono-Q ion exchange high performance liquid chromatography into four separate phosphodiesterase peaks: a cGMP-stimulated, two cAMP-specific Rolipram-sensitive and a cGMP-inhibited cardiotrope-sensitive peaks. Concanavalin A stimulated very specifically the activity of the two predominant cAMP-specific Rolipram sensitive peaks whereas it only slightly modified the cGMP-stimulated and the cGMP-inhibited forms. The present results strongly suggest that the Rolipram-sensitive cAMP PDE activity may play a key role in the control and regulation of mitogen-induced thymocyte proliferation.
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PMID:Concanavalin A stimulates the Rolipram-sensitive isoforms of cyclic nucleotide phosphodiesterase in rat thymic lymphocytes. 216 36

An extra copy of chromosome 21, a small chromosome or a specific segment of it, is the cause of the disorder known as Down's syndrome (DS). Genes mapped to this chromosome include superoxide dismutase-1 (SOD-1) along with other enzymes. Gene dosage effects have been shown for some of these enzymes, including SOD-1. Increased SOD-1 has been suggested to stimulate the cGMP-forming enzyme, guanylate cyclase (GC). In the present study we have used amnion cells from DS subjects and normal subjects in order to indirectly test the effects of SOD-1 on the cGMP metabolism. We have measured the cAMP and cGMP content, SOD-1 activity, GC activity and cGMP phosphodiesterase (G-PDE) activity in amnion cells from DS subjects and normal subjects, respectively. The levels of cGMP in DS amnion cells were lower than in normal cells, although the SOD-1 activity was higher in DS amnion cells. Furthermore, the GC activity and the G-PDE activity were found to be lower in the trisomic cells. Our results do not support the suggestion that SOD-1 has a stimulatory effect on the GC activity.
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PMID:Cyclic guanosine monophosphate metabolism in human amnion cells trisomic for chromosome 21. 216 49

In the inherited degenerative retinal disease of the rd mouse, rod cGMP levels rise above normal due to depressed cGMP-phosphodiesterase (cGMP-PDE) function a few days before degeneration begins. The subnormal activity of the cGMP-PDE may be due to a lesion in the enzyme itself, or in any of several proteins that regulate it. We have used a bovine cDNA for the alpha-subunit of cGMP-PDE to map its gene Pdea to mouse chromosome 18 at a distance of 21 centimorgans (cM) from the Mbp locus. Since the locus of the rd mutation is on mouse chromosome 5, a defect in the Pdea gene is ruled out as the cause of this inherited retinal degeneration.
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PMID:Genetic mapping demonstrates that the alpha-subunit of retinal cGMP-phosphodiesterase is not the site of the rd mutation. 216 32

The binding of radiolabelled cGMP to rod outer segment proteins has been investigated in mice, heterozygous for the recessive rd gene that leads to rod dysplasia. Two binding sites were detected, by Scatchard analysis, in a crude cGMP phosphodiesterase fraction, extracted with an EDTA wash from outer segments. Affinities were normal but the capacity of both was reduced 25-35%. Photoaffinity labelling with 3H-cGMP, followed by SDS PAGE and fluorography, suggested that cGMP PDE was the principal binding component in the extracts. If the finding reflects cGMP binding in situ, it might explain the 30-40% lower than normal level of cGMP found in the +/rd retina. Visual pigment has been regenerated in isolated normal and heterozygotic retinas by the application of active isomers of cis-retinal, and the time course of cGMP recovery to 'dark-adapted' levels monitored. The increase in the concentration of cGMP was significantly delayed as compared to that of rhodopsin. No differences in time course or kinetics of recovery were discerned between the two genotypes.
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PMID:Evidence for reduced binding of cyclic GMP to cyclic GMP phosphodiesterase in photoreceptors of mice heterozygous for the rd gene. 217 76

The content of cyclic nucleotides and activity cAMP- and cGMP-dependent PDE-ases have been studied in the rat liver and activity of NaF stimulated adenylate cyclase was studied in plasma membranes of the rat liver at late stages (2-5.5 months) of hepatocarcinogenesis induced by NDEA. A considerable decrease in the basal adenylate cyclase activity and NaF stimulated adenylate cyclase activity in plasma membranes of hepatomas in comparison with norm has been observed. During the hepatocarcinogenesis it was observed a decrease in the cAMP/cGMP ratio, an increase of the cAMP-dependent PDE-ase and a decrease in activity of cGMP-dependent PDE-ase in the rat hepatomas have been found.
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PMID:[The role of the components of the cyclic nucleotide system in N-nitrosodiethylamine-induced hepatic carcinogenesis in rats]. 217 96

In order to investigate the nature of Spleen deficiency and the mechanism of immunodepression due to Spleen deficiency and explore the pharmacological action of Chinese drugs of Yiqi Jianpi decoction (YQJP), the authors had established the rats model by administration Rhubarb. The preliminary results demonstrated that the symptoms manifested in rats were similar to those of Spleen deficiency syndrome. The changes of cyclic nucleotides in the spleen and plasma were unanimous. The cAMP level and the ratio of cAMP/cGMP decreased significantly while cGMP level increased significantly. Adenylate cyclase (AC) activity in the spleen reduced remarkably while cAMP-PDE activity had little changes. After the administration of YQJP, the symptoms of Spleen deficiency improved to normal extent. YQJP elevated the cAMP level, the ratio of cAMP/cGMP and AC activity while it lowered the cGMP level. The results showed that the changes of cyclic nucleotides level and the ratio of cAMP/cGMP were important targets of Spleen deficiency and that the action of YQJP followed the change of the ratio of cAMP/cGMP. The results of this study indicated that immunodepression of Rhubarb was due to depressing AC activity and reducing the ratio of cAMP/cGMP. The readjusting action of YQJP was concerned with AC system. This study supplied Spleen deficiency and YQJP with certain data in biochemical mechanism and pharmacological function.
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PMID:[Changes in cyclic nucleotides and its enzymes in the spleen and plasma of similar spleen deficiency rats induced by rhubarb and the readjusting function of yiqi jianpi decoction]. 217 77


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