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)

Human blood platelets were disrupted by ultrasonication, and the guanylate cyclase activity was determined in the 105,000 g supernatant. The guanylate cyclase preparation obtained in the absence of dithiothreitol (DTT) was characterized by a nonlinear dynamics of cGMP synthesis during incubation at 37 degrees C. The use of 0.2 mM DTT during platelet ultrasonication stabilized the guanylate cyclase reaction and did not influence the enzyme activity. With a rise in DTT concentration up to 2 mM the guanylate cyclase activity diminished. Sodium nitroprusside stimulated the enzyme; this effect was enhanced in the presence of DTT. The maximum guanylate cyclase activity was revealed at 4 mM Mn2+ or Mg2+ and with 1 mM GTP. In the presence of Mn2+ the enzyme activity was higher than with Mg2+. The apparent Km values for GTP in the presence of 4 mM Mn2+ and Mg2+ was 30 and 200 microM, respectively. At GTP/cation ratio of 1:4 the Km values for Mn2+ and Mg2+ were nearly the same (249 and 208 microM, respectively). It was assumed that besides being involved in the formation of the GTP-substrate complex, Mn2+ exerts a strong influence on guanylate cyclase by oxidizing the SH-groups of the enzyme.
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PMID:[Guanylate cyclase from human blood platelets]. 288 77

Receptor-mediated regulation of guanylate cyclase is well-studied in intact Dictyostelium discoideum cells, but study of the enzyme in cell-free preparations has hampered. A major obstacle has been that in vitro guanylate cyclase activity could be detected only in the presence of unphysiological concentrations of Mn2+-ions. In this paper we report the identification of a guanylate cyclase in D.discoideum cell homogenates that has high activity with Mg2+-GTP. The enzyme is activated by non-hydrolyzable ATP and GTP analogues and inhibited by submicromolar concentrations of Ca2+-ions. We suggest that the presently identified enzyme is regulated in intact cells via cell surface receptors. The compounds that modulated the enzyme activity in vitro may reflect physiologically relevant regulation mechanisms.
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PMID:A magnesium-dependent guanylate cyclase in cell-free preparations of Dictyostelium discoideum. 289 90

Human neutrophils were incubated with granulocyte-macrophage (GM)-CSF and examined for changes in second messenger systems. Twofold increases in cGMP but not cAMP were measured after 5 to 20 min with 100 U/ml GM-CSF. Guanylate cyclase activities in membrane and cytosol fractions were increased to the same extent whether measured in the presence of Mg2+ or Mn2+, or in the cytosol with Mg2+ + N-methyl-N'-nitro-N-nitroso-guanidine. Kinetic studies of the cytosol enzyme showed no changes in the Km values for Mg2+ and Mn2+dependent guanylate cyclase activities (0.91 and 0.022 mM, respectively), whereas Vm values were increased after treating intact cells with GM-CSF. Two peaks of guanylate cyclase activity were observed, one at 10 and another at 60 min after adding 100 U/ml GM-CSF, whereas only one peak at 5 min occurred with 1 U/ml. Adenylate cyclase activity was reduced by nearly 50% after adding 100 U/ml GM-CSF for 10 to 30 min. These effects were also seen in the presence of several hormonal and nonhormonal adenylate cyclase stimulators. In contrast, small increases in adenylate cyclase activity occurred after adding 1 U/ml GM-CSF. In experiments to examine the pathway of guanylate cyclase activation by GM-CSF, we observed no changes in inositol phosphates, intracellular calcium ion, or cytosolic protein kinase C. The augmentation of chemotactic peptide-induced superoxide production by GM-CSF concentrations, may be related to the effects of the higher levels of GM-CSF to stimulate late increases in guanylate cyclase or decreases in adenylate cyclase.
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PMID:Stimulation of guanylate cyclase activity and reduction of adenylate cyclase activity by granulocyte-macrophage colony-stimulating factor in human blood neutrophils. 289 92

Atriopeptin III is natriuretic, diuretic, and phosphaturic in the intact dog and relaxes vascular and nonvascular smooth muscle in vitro. The mechanism of the renal effects of atriopeptin remains ill defined but may include hemodynamic alterations and/or direct tubular effects. Since many peptide hormones act through changes in cyclic nucleotide formation, we examined the effect of synthetic atriopeptins on cAMP and cGMP accumulation in isolated glomeruli and proximal tubules from normal dog kidney. Synthetic atriopeptin produced a dose-related increase in cGMP in glomeruli with a Kact of 200 +/- 19 nM and a maximal activity of 64.1 +/- 6.3 pmol cGMP X mg prot-1 X 5 min-1. In the presence of 4 mM Mn2+ Kact was reduced to 19 +/- 2 nM with no change in maximal cGMP production (66.2 +/- 11.8 pmol cGMP X mg prot-1 X 5 min-1). Atriopeptin (1 microM) did not increase cGMP accumulation above basal levels in proximal tubule segments. The cAMP production of neither glomeruli nor proximal tubules was stimulated by atriopeptin. These studies demonstrate a dose-dependent stimulation of guanylate cyclase by atriopeptin in glomeruli but not in proximal tubule segments. In addition, atriopeptin neither stimulates nor inhibits cAMP accumulation in glomeruli or proximal tubules. These data suggest a major role for the renal effects of atriopeptin at the glomerular level, possibly through hemodynamic effects or changes in the glomerular ultrafiltration coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atriopeptin III increases cGMP in glomeruli but not in proximal tubules of dog kidney. 300 94

The effects of nitrates on Ca2+ increase and cyclic nucleotide content in human platelets were studied. Nitroglycerin, isosorbide dinitrate and sodium nitroprusside were found to inhibit the intracellular Ca2+ increase induced by the platelet activating factor, ADP and a stable thromboxane A2 analog--U46619. The inhibiting effect of sodium nitroprusside manifested itself at lower concentrations than those of nitroglycerin and isosorbide dinitrate. Nitroglycerin suppressed the Mn2+ entry into the cells and caused a 2-fold increase of the cGMP content which correlates with the calcium blocking activity. Methylene blue, a guanylate cyclase and glutathione reductase inhibitor, decreased the calcium blocking effect of nitroglycerin and its influence on the cyclic nucleotide content but failed to suppress the inhibitory effect of sodium nitroprusside. The data obtained suggest that the effects of nitrates on platelets are mediated by their influence on guanylate cyclase which leads to a cyclic nucleotide content increase and to a calcium blocking effect.
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PMID:[Calcium-blocking effect of nitro compounds in human platelets: correlation with changes in the cyclic guanosine monophosphate level]. 303 39

A guanylate cyclase preparation partially purified from supernatant of a pig lung extract was subjected to affinity chromatography on an Agarose-GTP column. The major portion of the cyclase activity was adsorbed on the column and then eluted with 50 mM EDTA and 0.5 M KCl, whereas the fractions non-adsorbed on the column contained a factor which enhanced the cyclase activity. Addition of the activating factor to a cyclase reaction mixture increase the enzyme activity without a time lag, and this enhancement by the factor was dose-dependent. With concomitant presence of cyclase and the factor in the reaction mixture the apparent Km value for GTP-Mn2+ of the enzyme was 56 microM, this value being the same as in absence of the factor, however, here the maximum velocity increased 4-fold. The factor was nondiffusable, heat-labile, partially sensitive to trypsin, and resistant to acid or alkali. As estimated by gel filtration, this factor had an apparent molecular weight of 85 000.
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PMID:Involvement of a macromolecular activating factor in activity of guanylate cyclase partially purified from supernatant of a pig lung extract. 610 82

The particulate fraction from murine plasmocytoma cells contained 90 per cent of the total guanylate cyclase activity. Triton X-100 produced a 6 fold stimulation of guanylate cyclase activity in plasma membrane enriched fractions obtained by zonal centrifugation. Isolated inside out (10) vesicles contained 9 times more activity than rightside out (RSO) vesicles. This difference was abolished by Triton X-100 treatment of the vesicles indicating that the catalytic site of guanylate cyclase is located on the inner face of the plasma membrane. Kinetic studies of membranous guanylate cyclase showed that optimal activity was found with manganese. Only 20 per cent of this activity was obtained with magnesium. The Km for GTP with magnesium (1.4 mM) was about 7 fold greater than with manganese (0.2 mM). Positive cooperativity was obtained in both cases and the Hill coefficients were 1.8 for manganese and 1.6 for magnesium. Physiological concentrations of ATP were found to inhibit both manganese and magnesium supported activities indicating a possible regulatory mechanism for this nucleotide in vivo.
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PMID:Manganese and magnesium dependent properties and inner plasma membrane surface localization of guanylate cyclase from murine plasmocytoma cells. 610 85

Adenylate cyclase from the guinea-pig pancreas was activated in a dose-dependent manner by both secretin and cholecystokinin-pancreozymin, but in contrast with results in other species the hormones were approximately equipotent. All other hormones and transmitter substances tested were without any effect on adenylate cyclase activity. Guanylate cyclase activity was shown to have both particulate and supernatant components in the guinea-pig pancreas. The particulate enzyme, but not the supernatant enzyme, was markedly activated by Triton X-100, and most of the induced activity was released into the supernatant. The supernatant enzyme was specifically Mn2+-dependent, but, even though Mn2+ was maximally effective at a concentration of 3 mM, activity could be raised further by increasing Ca2+ concentration. The particulate enzyme, by contrast, was relatively Mn2+-independent. Activity of the particulate guanylate cyclase was enhanced by phosphatidylserine. The supernatant enzyme displayed classical Michaelis-Menten kinetics, but the particulate enzyme deviated markedly from such kinetics. Under none of the conditions used was any significant activation of guanylate cyclase observed with any of the secretogen hormones or transmitter substances.
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PMID:The metabolism of cyclic nucleotides in the guinea-pig pancreas. Adenylate cyclase and guanylate cyclase. 610

In vivo injections of gibberellic acid, a potent plant growth hormone, are known to increase the growth of animals as well as plants. Investigation into gibberellic acid's growth promoting mechanism in animals at the cellular level focused on guanylate cyclase (E.C.4.6.1.2.), an enzyme known to be associated with growth. Gibberellic acid enhanced the activity of rat lung guanylate cyclase over a concentration range of .00001 mM to 1 mM with no stimulation being observed at .000001 mM. Varying the concentration of the guanylate cyclase co-factor manganese had no effect on gibberellic acid's enhancement of guanylate cyclase activity. Since human and rat growth hormones also enhance guanylate cyclase activity, it appears that at cellular level the mechanism of action of growth promoting hormones may include a common process that involves enhancement of guanylate cyclase activity.
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PMID:Gibberellic acid, a plant growth hormone, enhances mammalian guanylate cyclase activity. 610 50

Most of the particle-bound guanylate cyclase of pigeon heart muscle, which is the predominant form of the enzyme in this tissue, co-purified with calcium pump system of the sarcoplasmic reticular fraction. Specific enzyme activity at 37 degrees C ranged up to 0.67 nmol/mg of protein/min. The K0.5 values for MnCl2, Mn2+ free, and GTP were found to be 0.72, 0.076, and 0.057 mM, respectively. Mg2+ activates and Ca2+ inhibits the enzyme in the presence of Mn2+, whereas carbamylcholine was without effect. The ratio of guanylate cyclase to adenylate cyclase activity was found to be 12:1 in the sarcoplasmic reticulum fraction and 0.5:1 in the sarcolemal fraction. Our findings suggest that the major portion of guanylate cyclase in pigeon myocardium is not directly activated by the interaction of hormones and neurotransmitters with their receptors in the cell surface membrane.
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PMID:Subcellular distribution and some properties of particulate guanylate cyclase of pigeon myocardium. 610 52


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