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)

Guanylate cyclase in rat cerebellum was investigated on the light microscopical level with guanylyl imidodiphosphate as substrate. Several attempts for activation of enzymatic activity and delimitation to other enzymes were made by sodium azide, aminophylline, sodium fluoride and dithioerythrole. The localization was similar but less strong compared to adenylate cyclase (Poeggel and Luppa 1984) and differs in behaviour to the above mentioned substances. Nucleotide pyrophosphatases seem to play an unimportant role in guanylyl imidodiphosphate conversion, while alkaline phosphatase is possibly of more importance. A light microscopical demonstration of guanylate cyclase by its enzymatic activity must be considered with caution. Main reasons are the low activity and therefore the great importance of interfering enzymes with high activities.
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PMID:Attempts for light microscopical demonstration of guanylate cyclase activity in rat cerebellum. 287 7

Cell fractionation studies have been performed, in order to obtain insight into the subcellular distribution of Dictyostelium adenylate cyclase and guanylate cyclase and also to provide a starting point for further study and isolation of these enzymes and their regulatory components. Adenylate cyclase and cAMP receptors were found in the same membrane fractions, but were distributed different from the plasma membrane marker alkaline phosphatase. Guanylate cyclase was partially soluble, partially particulate. In isopycnic gradients, particulate guanylate cyclase was present in other fractions than cAMP receptors and adenylate cyclase, but in similar ones to alkaline phosphatase. These observations are consistent with the hypothesis that cell-surface cAMP receptors and adenylate cyclase interact via a membrane-bound G-protein, whereas the receptors activate guanylate cyclase via a cytosolic factor. The adenylate cyclase activity in membranes obtained by sucrose gradient centrifugation was retained in the presence of various detergents, while with the same detergents the activity of particulate guanylate cyclase was lost. This adenylate cyclase was solubilized as assessed by gel filtration and centrifugation experiments, and it behaved heterogeneous in fractionation studies. In gel filtration, the major component eluted at a position corresponding to a Stokes radius of 4-7 nm. A purification of about 70-fold as compared to the cell homogenate was obtained by affinity chromatography of adenylate cyclase on ATP-Sepharose. We conclude that cell fractionation provides useful starting material for isolation and further study of Dictyostelium adenylate cyclase.
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PMID:Cell fractionation, detergent sensitivity and solubilization of Dictyostelium adenylate cyclase and guanylate cyclase. 288 13

Guanylate cyclase is dephosphorylated in response to the interaction of egg peptides with a spermatozoan surface receptor (Suzuki, N., Shimomura, H., Radany, E. W., Ramarao, C. S., Ward, G. E., Bentley, J. K., and Garbers, D. L. (1984) J. Biol. Chem. 259, 14874-14879). Here, the phosphorylated form of guanylate cyclase was purified to apparent homogeneity from detergent-solubilized spermatozoan membranes by the use of GTP-agarose, DEAE-Sephacel, and concanavalin A-Sepharose chromatography. To prevent dephosphorylation of the enzyme during purification, glycerol (35%) was required in all buffers. Following purification, a single protein-staining band of Mr 160,000 was obtained on sodium dodecyl sulfate-polyacrylamide gels. The final specific activity of the purified enzyme was 83 mumol of cyclic GMP formed/min/mg of protein at 30 degrees C, an activity 5-fold higher than that observed with the purified, dephosphorylated form of guanylate cyclase. A preparation containing protein phosphatase from spermatozoa, or highly purified alkaline phosphatase (from Escherichia coli), catalyzed the dephosphorylation of the enzyme; this resulted in a subsequent decrease in guanylate cyclase activity and a shift in the Mr from 160,000 to 150,000. The phosphate content of the high Mr form of the enzyme was 14.6 mol/mol protein whereas the phosphate content of the low Mr form was 1.6 mol/mol protein. All phosphate was localized on serine residues. The Mr 160,000 form of guanylate cyclase demonstrated positive cooperative kinetics with respect to MnGTP while the Mr 150,000 form displayed linear, Michaelis-Menten type kinetics. The phosphorylation state of the membrane form of guanylate cyclase, therefore, appears to dictate not only the absolute activity of the enzyme but also the degree of cooperative interaction between catalytic or GTP-binding sites.
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PMID:Purification and properties of the phosphorylated form of guanylate cyclase. 289 12

Cytochemical differentiation between blood and lymphatic endothelium has been studied only in microvessels; 5'-nucleotidase (5'Nase) has been reported to be specific for lymphatic and alkaline phosphatase (ALPase) for blood endothelium. Adenylate and guanylate cyclase (AC and GC) have recently been proposed as lymphatic endothelial markers, but conflicting data exist. This study was designed to verify the presence of these enzymes in the endothelium of large vessels and to determine whether they are retained in endothelial cells (ECs) in culture. Segments of bovine mesenteric arteries, veins, and lymphatic collectors, and EC cultures obtained by collagenase treatment of the same vessels, were assayed for 5'Nase, ALPase, AC, and GC, and were observed by transmission electron microscopy. We found ALPase activity in blood and lymphatic vessels, and this was the only enzyme activity consistently retained under culture conditions. 5'Nase was found in lymphatic but not in blood endothelium, as previously reported for microvessels. AC and GC activity was found in blood but not in lymphatic endothelium. Hence, ALPase is not a useful marker to differentiate blood from lymphatic endothelium in large vessels, whereas 5'Nase is specific for lymphatic and AC and GC for blood endothelium. It is not clear why these enzyme activities are not expressed in culture.
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PMID:Cytochemical differentiation between blood and lymphatic endothelium: bovine blood and lymphatic large vessels and endothelial cells in culture. 791 6

The localization of some membrane-associated enzymes such as alkaline phosphatase, 5'-nucleotidase, glucose-6-phosphatase, Na+,K(+)-adenosine triphosphatase, adenylate cyclase and guanylate cyclase in the Merkel cell-axon complexes, trigeminal ganglia and the principal trigeminal sensory nucleus of the cat was determined at light and electron microscopic level using cytochemical techniques. In the sinus hair follicles (vibrissae), the reaction end product marking alkaline phosphatase and adenosine triphosphatase activities was visualized on the axons running through external follicle epithelium and the 5'-nucleotidase, adenylate- and guanylate cyclase positive reaction was seen to stain the plasma membranes of Merkel cells. In the trigeminal ganglia, the strongest alkaline phosphatase and adenosine triphosphatase activities showed the corresponding areas between the ganglion and satellite cells. 5'-nucleotidase activity was more intense on the neurilemmas and the surrounding glial plasma membranes. In the principle sensory trigeminal nucleus, the central neurons exhibited an intense alkaline phosphatase, 5'-nucleotidase and adenosine triphosphatase activities and much smaller amount of reaction product for adenylate cyclase and guanylate cyclase was observed. In conclusion, membrane-bound enzymes could be histo- and cytochemically demonstrated in all components of primary trigeminal afferent units. Our results have confirmed that the receptor function and the nerve impulses conductance need an intensive molecular and cation exchange, and energy supply.
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PMID:Primary trigeminal afferent neuron of the cat: I. Studies on membrane-bound enzyme histochemistry. 798 69

The permeability of higher molecular weight substances was investigated in mouse chorioallantoic labyrinthine hemotrichorial placenta, using horseradish peroxidase as a tracer. At the same time, ultrastructural localizations of some important enzymes, such as alkaline phosphatase (ALP), acid phosphatase (ACP), Ca(++)-ATPase and guanylate cyclase were elucidated in this organ by means of the enzyme-cytochemical technique. Peroxidase easily entered the space between layers I and II, and no penetration of this tracer beyond layer II was observed. The reaction products for ALP activity were found mainly on the maternal side of the plasma membrane of the layer II trophoblast. ACP activity was confined to the lysosomes of this layer II cell. In short, peroxidase stopped at the cell surface of the layer II trophoblast, and both ALP and ACP coexisted in this layer II cell. These observations strongly suggest that the layer II trophoblast, especially the surface plasma membrane of this cell, may have an important role in regulating the materno-fetal transfer of substances in mouse chorioallantoic placenta.
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PMID:Studies on the permeability and enzyme-cytochemistry of the mouse hemotrichorial placenta. 813 78

Regulation of intestinal epithelial differentiation is critical to normal function, malignant transformation, and healing. However, the intracellular regulation of intestinal epithelial differentiation is incompletely understood. We studied the effects of intracellular cyclic AMP and cyclic GMP on brush border enzyme activity in the human Caco-2 intestinal epithelial cell using pharmacologic agonists and antagonists of cAMP and cGMP mediated pathways as probes. The stable cyclic nucleotide analogs dibutyryl cAMP and dibutyryl cGMP selectively decreased Caco-2 dipeptidyl dipeptidase specific activity while increasing alkaline phosphatase. The inhibitors of adenylate and guanylate cyclase KT5720 and KT5823 each exerted the opposite effects. Combinations of dibutyryl cAMP and dibutyryl cGMP demonstrated synergistic effects on each brush border enzyme but KT5720 and KT5823 were less than additive. Thus, cAMP and CGMP may regulate human intestinal epithelial differentiation by interacting pathways.
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PMID:Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides. 861 19

C-type natriuretic peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial natriuretic peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [3H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of "bone natriuretic peptide system."
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PMID:C-type natriuretic peptide as an autocrine/paracrine regulator of osteoblast. Evidence for possible presence of bone natriuretic peptide system. 866 Mar 52

The exposure of human platelets to prostaglandin H2 analogue (PGH2, U46619) induces homologous desensitization and a concomitant adenylate cyclase (AC) sensitization. We demonstrate the involvement of phospholipase C (PLC) in this enzyme sensitization. Pre-incubation of platelets with neomycin, a PLC activity inhibitor, prevented AC sensitization but not PGH2/thromboxane (Tx)A2 receptor desensitization. PGH2/TxA2 receptor desensitization, although necessary, is not sufficient to induce AC sensitization, since neomycin, which prevents AC sensitization, failed to prevent receptor desensitization. Inositol phosphate formation, determined in parallel, was also inhibited. Interestingly, no guanylate cyclase sensitization was noted, suggesting a specific relationship between PGH2/TxA2 receptor desensitization and AC sensitization. In addition, using alkaline phosphatase, a dephosphorylating enzyme, and the tyrosine kinase inhibitor erbstatin, we examined the role of phosphorylation-dephosphorylation on AC sensitization. Effectively, alkaline phosphatase, which has no effect by itself, enhances the cAMP production triggered by prostacyclin in control but not in desensitized platelets. In contrast, erbstatin failed to modify this synthesis, indicating the non-involvement of tyrosine kinase pathway in this process. Our results indicate that the AC sensitization was mediated by PLC and also suggest the participation of other mechanisms, including phosphorylation-dephosphorylation processes. This specific enzyme sensitization may be relevant for the in vivo modulation of platelet activation, in different thrombotic diseases with an increased TxA2 generation.
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PMID:Signal transduction involved in the platelet adenylate cyclase sensitization associated with PGH2/TxA2 receptor desensitization. 935 23

Nitric oxide is a gas radical regulating cell behaviour in the cardiovascular, immune, and central nervous systems. It has now been established as an important signalling molecule in bone. However, the effects of this gas radical on osteoblastic function are still unclear; in fact, while NO seems to be involved in anabolic processes mediated by mechanical strain, sex hormones and fracture healing, it also mediates catabolic processes in response to inflammation. We show here that a slow and moderate release of nitric oxide stimulates the replication of primary rat osteoblasts and alkaline phosphatase activity, while a rapid release and high concentrations of NO inhibit proliferation and induce apoptosis. We demonstrate that both the stimulatory and apoptosis-inducing effects of NO on primary osteoblasts are mediated by the second messenger cGMP, since both are abolished by the guanylate cyclase inhibitor ODQ.
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PMID:The biphasic effects of nitric oxide in primary rat osteoblasts are cGMP dependent. 1091 63


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