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)

Cyclic nucleotide phosphodiesterase [EC 3.1.4.17] was examined in tetrahymena pyriformis strain NT-1. Enzymic activity was associated with the soluble and the particulate fractions, whereas most of the cyclic GMP phosphodiesterase activity was localized in the soluble fraction; the activities were optimal at pH 8.0-9.0. Although very low activities were detected in the absence of divalent cations, they were significantly increased by the addition of either Mg2+ or Mn2+. A kinetic analysis of the properties of the enzymes yielded 2 apparent K(m) values ranging in concentration from 0.5 to 50 micron and from 0.1 to 62 micron for cyclic AMP and GMP, respectively. A Ca2+ -dependent activating factor for cyclic nucleotide phosphodiesterase was extracted from Tetrahymena cells, but this factor did not stimulate guanylate cyclase [EC 4.6.1.2] activity in this organism. On the other hand, tetrahymena also contained a protein activator which stimulated guanylate cyclase in the presence of Ca2+, although this activator did not stimulate the phosphodiesterase. The results suggested that Tetrahymena might contain 2 types of Ca2+ -dependent activators, one specific for phosphodiesterase and the other for guanylate cyclase.
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PMID:Studies on cyclic nucleotide metabolism in Tetrahymena pyriformis: partial characterization of cyclic AMP- and cyclic GMP-dependent phosphodiesterases. 610 21

In neurosecretosomes, isolated from ox neurohypophyses, both guanylate and adenylate cyclase activity was shown to be predominantly membrane-bound. Membrane-bound adenylate cyclase was inhibited by increasing the ionized calcium concentration from 10(-7) M to 10(-5) M, but was stimulated by calmodulin in the presence of 10(-7) M and 10(-5) M ionized calcium. In contrast, neither calcium ions nor calmodulin affected the activity of membrane-bound guanylate cyclase. Soluble cyclic AMP and cyclic GMP phosphodiesterase activities increased with increasing ionized calcium concentration (10(-7) M to 10(-3) M). At 10(-7) M ionized calcium concentration, both soluble phosphodiesterase activities were stimulated by calmodulin. Both the membrane-bound phosphodiesterase activities were inhibited by a high ionized calcium concentration (10(-3) M) and not affected by calmodulin.
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PMID:Effects of Ca2+ and calmodulin on cyclic nucleotide metabolism in neurosecretosomes isolated from ox neurohypophyses. 611 72

Levels of cGMP phosphodiesterase, guanylate cyclase, and GTPase activities were determined in homogenates of chick pineal glands. Only small variations in vivo were observed with glands removed at different times of the day from birds under a standard cycle of illumination. Glands cultured under the cycle of illumination from late in the photoperiod showed a progressive loss of about half the phosphodiesterase activity in 24 h, and an increase of roughly 75% in GTPase activity within 12 h. No simple correlations were found between variations in levels of enzyme activity and the diurnal cycles in pineal content of cGMP and level of serotonin N-acetyltransferase (NAT) activity. However, onset of rapid increases in 3',5'-cyclic GMP (cGMP) content and NAT activity was correlated with a transient decrease of about 30% in the phosphodiesterase activity, both in vivo and in culture. Further, known inhibitors of phosphodiesterase activity previously shown to elicit increase of cGMP content and marked elevation of NAT activity in cultured glands only inhibited phosphodiesterase activity of homogenates by 25-30%. It was therefore concluded that the transient decrease in level of phosphodiesterase may facilitate onset of increase in pineal cGMP content. However, it seems improbable that changes in pineal content of enzymes of guanine nucleotide metabolism are essential to regulation of diurnal cycles in cGMP content or level of NAT activity.
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PMID:Enzymes of guanine nucleotide metabolism and the diurnal cycle in cGMP content of the chick pineal gland. 613 5

Evidence for the presence of multiple cyclic GMP (cGMP) systems in the vertebrate retina is examined. Levels of this cyclic nucleotide are characteristically high in the photoreceptor cell, whereas in the inner retina they are similar to those found in other areas of the central nervous system. Guanylate cyclase and cGMP phosphodiesterase show a similar uneven distribution, with very high levels of activity in outer segments. At least three forms of guanylate cyclase, one of which may be unique to the photoreceptor cell, have been described. Similarly, differences in the regulation of cGMP phosphodiesterase within localized areas of retina indicate the existence of multiple forms of this enzyme. Factors that influence cGMP levels also have regionally variable effects. Light adaptation leads to reduced cGMP levels in the distal retina, whereas inner retina layers do not show parallel changes. Calcium suppresses the formation of cGMP in photoreceptors, but has no effect or stimulates cGMP formation in the inner retina. Cellular depolarization appears to reduce levels of cGMP in photoreceptors and increases it in the inner retina. Furthermore, endogenous proteins whose phosphorylation is apparently controlled by cGMP seem to be localized to specific retinal cells or subcellular organelles. These data lead to the conclusion that multiple cGMP systems exist in the retina, each with a distinct location and function.
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PMID:Cyclic GMP systems in the retina. 613 83

The cellular distribution of guanylate cyclase (EC 4.6.1.2), guanosine 3',5'-phosphate (cyclic GMP), cyclic GMP-dependent protein kinase (EC 2.7.1.38), and cyclic GMP phosphodiesterase (EC 3.1.4.17) have been examined in the rostral rat caudate-putamen complex. Immunofluorescent staining for guanylate cyclase, cyclic GMP, and cyclic GMP-dependent protein kinase in fresh frozen caudate-putamen tissues is analogous to the immunoperoxidase localization in perfusion-fixed striatal slices. Homologous immunoreactivity in the cytoplasm and processes of ovoid and rounded neurons, 15-20 microns in diameter can be seen for these three components of the cyclic GMP system. Immunoreactive neurons are uniformly distributed throughout the caudate-putamen complex of all experimental tissue examined. Occasional large neurons, greater than 25 microns in diameter, in the ventral region of the striatum show immunoreactivity. Enzyme histochemical determination of the activities of guanylate cyclase and cyclic GMP phosphodiesterase show the medium-sized neuronal population (15-20 microns) contain hydrolytic activity for these proteins. Large- to medium-sized capillaries demonstrate guanylate cyclase synthetic activity, but the endothelial cells do not exhibit immunohistochemical staining. This suggests that physiological activity of an enzyme cannot be completely discerned through application of immunohistochemical procedures. Additionally, enzymatically detected guanylate cyclase histochemical activity was not uniformly distributed throughout the striatal neuropil. Enzyme histochemical detection of cyclic GMP phosphodiesterase demonstrates homologous cellular staining to guanylate cyclase enzymatic reactivity. The activity of the phosphodiesterase hydrolytic enzyme could be detected evenly distributed throughout the neuropil within cells 15-20 microns in diameter, analogous in cytoarchitecture to immunohistochemically visualized guanylate cyclase, cyclic GMP, and protein kinase elements. Ultrastructural examination of rat caudate-putamen demonstrates that the immunoreactivity for the components of the cyclic GMP system is predominantly distributed within the medium-spiny neuron subtype of this structure. Occasional aspiny neurons demonstrate peroxidase immunoreactivity for the cyclase, cyclic GMP, and the protein kinase, as does the luminal surface of capillary endothelial cells. The subcellular distribution of the antigenic determinants for these three elements and the hydrolytic activity of the phosphodiesterase enzyme show proximity to one another and are confined to the postsynaptic region of asymmetrical, but not symmetrical, terminal boutons. The asymmetrical terminal population of the caudate-putamen is derived from striatal afferents from the neocortex, intralaminar thalamus, and substantia nigra, and to a lesser extent the intrinsic striatal circuitry.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distribution of components of the guanosine 3',5'-phosphate system in rat caudate-putamen. 613 69

Changes have been revealed in the function of cyclic GMP system of thymus and liver of irradiated (8 Gy) mice. In the thymus the cGMP level increased during the first 60 min following irradiation. In the liver the concentration of cGMP exhibited two peaks: 30 min and 24 hr after irradiation. The changes observed in the cGMP level are connected with the increased guanylate cyclase activity of thymocytes and liver of irradiated mice and, less likely, with changes in the activity of cGMP phosphodiesterase of these tissues.
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PMID:[Postirradiation changes in the cGMP system of the mouse thymus and liver]. 613 42

The effects of a novel compound, 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), on cyclic nucleotide metabolism and in vitro aggregation of human platelets were investigated. The concentrations of MY-5445 producing 50% inhibition of human platelet aggregation induced by 3 microM ADP, 3 micrograms/ml of collagen and 100 micrograms/ml of arachidonic acid were 0.07, 0.02 and 0.17 microM, respectively. Addition of MY-5445 significantly elevated cyclic GMP content in human platelets but had no effect on cyclic AMP content, suggesting that the drug affects principally the cyclic GMP metabolism in the platelet. Although MY-5445 had no effect on either adenylate cyclase or guanylate cyclase activity, it inhibited specifically human platelet cyclic GMP phosphodiesterase which was separated from cyclic AMP phosphodiesterase by diethylaminoethyl-cellulose column chromatography. The inhibitory effect of MY-5445 on cyclic GMP phosphodiesterase was also demonstrated by direct binding of the enzyme to MY-5445 coupled Sepharose, which was a useful tool for purifying the cyclic GMP phosphodiesterase from human platelet. These results would suggest that MY-5445 inhibits human platelet aggregation by increasing cyclic GMP content and that it provides a useful probe for elucidating the role of cyclic GMP in platelet aggregation.
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PMID:Effect of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of cyclic GMP phosphodiesterase, on human platelet aggregation. 614 Dec 86

Cyclic guanosine 3'5'-monophosphate was isolated and purified from Mycobacterium smegmatis TMC 1515 using ion exchange chromatography. It was characterized by thin layer chromatography and radioimmunoassay. Guanylate cyclase and cGMP phosphodiesterase were detected in the cytosolic and particulate (37,000 X g pellet) fractions respectively. On the basis of our observations, cGMP appears to play a dual role (i) at the time of induction of cell proliferation and (ii) protects the bacteria against unfavourable surroundings during stationary phase of the growth. This is the first report demonstrating presence of cGMP, guanylate cyclase and cGMP phosphodiesterase in mycobacteria.
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PMID:Characterization and metabolism of cyclic guanosine 3'5'-monophosphate in Mycobacterium smegmatis. 614 17

Mepacrine, a phospholipase A2 inhibitor, caused concentration-dependent elevations of cyclic GMP levels without changing cyclic AMP levels in washed rabbit platelets. Mepacrine (100 microM) increased cyclic GMP levels to a peak (25-fold of basal level) within 4 min. Mepacrine had no effect on platelet guanylate cyclase and cyclic AMP phosphodiesterase but selectively inhibited cyclic GMP phosphodiesterase, indicating that mepacrine may elevate platelet cyclic GMP levels as a result of inhibiting cyclic GMP breakdown. In addition, mepacrine accelerated the disaggregation of platelets which had been aggregated maximally by ADP. This effect was associated with elevated cyclic GMP levels. Likewise, sodium nitroprusside and sodium ascorbate, which also elevate platelet cyclic GMP levels, caused marked disaggregation. The increases in cyclic GMP levels with these agents were well correlated with the extent of disaggregation, suggesting that cyclic GMP may mediate a process opposing platelet aggregation and that the mepacrine-induced acceleration of disaggregation may be mediated by cyclic GMP.
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PMID:Mepacrine-induced elevation of cyclic GMP levels and acceleration of reversal of ADP-induced aggregation in washed rabbit platelets. 614 64

A 26 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) relaxed isolated rabbit aortic segments in which the endothelium was either intact or functionally destroyed. The relaxations were temporally associated with increases in levels of cGMP with no change in the levels of cAMP. The ANF-induced increases in cGMP were also observed in aortic segments pretreated with calcium-free buffer or the cGMP phosphodiesterase inhibitor M&B 22,948. Qualitatively similar results were obtained for sodium nitroprusside. ANF selectively activated particulate guanylate cyclase, having no effect on the soluble form of the enzyme. Thus, the direct (endothelium-independent) vasodilator effect of ANF may be mediated via increased tissue levels of cGMP. ANF appears to increase vascular cGMP levels by activation of particulate guanylate cyclase.
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PMID:Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. 615 Apr 86


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