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)

Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants.
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PMID:Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations. 1 19

Some properties of guanylate cyclase, which was solubilized from the rabbit heart washed particles by the treatment with Triton X-100, were investigated. The solubilized enzyme activity was stimulated by Mg2+ in the presence of low (subsaturating) Mn2+ (GTP is greater than Mn2+); under these conditions, Ga2+ was inhibitory. At subsaturating MnGTP and free Mn2+, the solubilized enzyme was markedly stimulated by MnGDP and MnATP; CaGTP on the other hand, was inhibitory. These results are consistent with the view that the particulate guanylate cyclase may exist in the cell as a metalloenzyme with tightly bound Mn2+ and that Mg2+ supports its catalysis while Ca2+ as well as nucleotides may exert regulatory effects on its activity.
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PMID:Interactions of divalent cations and nucleotides with solubilized cardiac guanylate cyclase. 1 29

Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues.
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PMID:Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. 1 94

Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity.
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PMID:[Proof of guanylate cyclase activity in the coronary artery of cattle]. 1 86

Cyclic nucleotide concentrations and guanylate cyclase activity were measured in regenerating rat liver. Previous work has shown that in livers of partially hepatectomized rats the activity of a membrane-bound guanylate cyclase increases considerably during the early replicative phase [Kimura & Murad (1975) Proc. Natl. Acad. Sci. U.S.A.72, 1965-1969; Goridis & Reutter (1975) Nature (London) 257, 698-700]. Over the same time period after partial hepatectomy, increased tissue concentrations of cyclic GMP were found when the rats were killed under pentobarbital anaesthesia, but not when anaesthesia was omitted. The results obtained on hepatectomized livers were compared with the changes in guanylate cyclase activity and cyclic nucleotide concentrations during the response to galactosamine treatment. Here, a peak of guanylate cyclase activity and of cyclic GMP concentrations occurred at 8h, that is before the beginning of the proliferative response. Both parameters were normal at the time of increased DNA synthesis. There does not, therefore, seem to be a consistent correlation between changes in guanylate cyclase activity or concentrations of cyclic GMP and an increase in liver DNA synthesis. A modest rise in cyclic AMP concentrations was found, however, in livers of galactosamine-treated rats, which was coincident with the time of DNA synthesis.
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PMID:Guanylate cyclase activity and cyclic nucleotide concentrations during liver regeneration after experimental injury. 1 46

The effect of guanosine on insulin secretion, adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans was investigated. Guanosine (1-100 micron) inhibited glucose, tolbutamide, theophylline and prostaglandin E2-stimulated insulin secretion although it failed to affect glucagon stimulated secretion. Prostaglandin E2-stimulated adenylyl cyclase activity of islets was inhibited by guanosine although guanosine had no effect on basal, fluoride, glucagon or GTP-stimulated activity. Guanosine markedly decreased basal guanylyl cyclase activity of islets. These results suggest that guanosine may affect insulin release by inhibiting adenylyl and guanylyl cyclase activities in the beta-cell thereby decreasing the intracellular concentrations of cyclic nucleotides. This effect may be important in modulating the secretory response of the islets to a variety of hormonal agents.
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PMID:Effects of guanosine on insulin secretion and adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans. 1 8

On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre-or post-synaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intrcellular injection techniques should minimize this particular problem, although possibly at the expense of new diffulties. Prio blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Utimately, the developement of highly specific inhibitor for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the action of cyclic GMP and the role of its synthesizing enzyme, guanylate cyclase. The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.
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PMID:The role of cyclic nucleotides in the CNS. 1 46

Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences.
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PMID:Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle. 1 16

Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal, and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 at 4 degrees but re-exposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine, and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. We propose that various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds.
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PMID:Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. 2 Jun 23

Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity of human platelet homogenates was stimulated by the addition of phospholipase A2 or unsaturated fatty acids such as oleic, vaccenic, linoleic, linolenic, eicosenoic, eicosadienoic, and arachidonic acids. The addition of lipoxidase potentiated the fatty acid-induced stimulation of guanylate cyclase purified by DEAE-cellulose column chromatography. The extent of the stimulation was dependent on the concentration of the oxidized form of these fatty acids (peroxides). Saturated fatty acids such as stearic and arachidic acids had no effect on the guanylate cyclase activity in the presence or absence of lipoxidase, indicating that human plateletguanylate cyclase is stimulated by unsaturated fatty acid peroxides rather than by fatty acids. Hemoglobin prevented the enzyme stimulation produced by low concentrations of fatty acid peroxides, but enhanced stimulation of the enzyme activity with high concentrations of fatty acid peroxides. 2-Mercaptoethanol, dithiothreitol, and N-ethylmaleimide inhibited the guanylate cyclase activities both in the presence and absence of unsaturated fatty acidperoxide. The stimulation of guanylate cyclase activity by unsaturated fatty acid peroxidesis attributed to oxidation of sulfhydryl residues of the enzyme protein.
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PMID:Stimulation of human platelet guanylate cyclase by unsaturated fatty acid peroxides. 2 Jun 30


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