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)

The effects of a variety of agents on guanylate cyclase activity were tested in broken cell preparations of mammary glands from midpregnant mice. Of the agents tested, only phospholipase A, triton X-100, and an impure egg lysolecithin preparation enhanced the activity of guanylate cyclase in mammary gland homogenates; other agents, including sodium azide and phospholipase C, and purified egg lysolecithin had no effect. Phospholipase A increased the activity of guanylate cyclase in the 150,000 g pellet fractions of mammary gland homogenates, bud did not consistently enhance guanylate cyclase in the 150,000 g supernatant fractions. Phospholipase A did not appear to enhance guanylate cyclase activity by solublizing the enzyme from the 150,000 g pellet. Triton X-100, in contrast, appeared to act by solubilizing guanylate cyclase from the material present in the 150,000 g pellet. Triton X-100 increased by several fold guanylate cyclase activity in the tissue homogenates and the 150,000 g pellets, but did not consistently enhance enzyme activity in the 150,000 g supernatant. Triton X-100 had no effect on the apparent Km of guanylate cyclase.
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PMID:Effects of phospholipase A and triton x-100 on guanylate cyclase activity in mammary gland homogenates from mice. 2 72

Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) was purified 2250-fold from the synaptosomal soluble fraction of rat brain. The specific activity of the purified enzyme reached 41 nmol cyclic GMP formed per min per mg protein at 37 degrees C. In the purified preparation, GTPase activity was not detected and cyclic GMP phosphodiesterase activity was less than 4% of guanylate cyclase activity. The molecular weight was approx. 480 000. Lubrol PX, hydroxylamine, or NaN3 activated the guanylate cyclase in crude preparations, but had no effect on the purified enzyme. In contrast, NaN3 plus catalase, N-methyl-N'-nitro-N-nitrosoguanidine or sodium nitroprusside activated the purified enzyme. The purified enzyme required Mn2+ for its activity; the maximum activity was observed at 3-5 mM. Cyclic GMP activated guanylate cyclase activity 1.4-fold at 2 mM, whereas inorganic pyrophosphate inhibited it by about 50% at 0.2 mM. Guanylyl-(beta,gamma-methylene)-diphosphonate and guanylyl-imidodiphosphate, analogues of GTP, served as substrates of guanylate cyclase in the purified enzyme preparation. NaN3 plus catalase or N-methyl-N'-nitro-N-nitrosoguanidine also remarkably activated guanylate cyclase activity when the analogues of GTP were used as substrates.
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PMID:Purification and properties of guanylate cyclase from the synaptosomal soluble fraction of rat brain. 2 67

The relationship between the subcellular distribution of guanylate cyclase and tissue guanosine-3',5'-cyclic monophosphate (cGMP) levels was investigated in rat testes after surgically induced unilateral cryptorchidism. Placement of one of a testis pair in the abdominal cavity results in loss of testicular weight and function in the abdominal testis whereas the remaining scrotal testis appears to be functionally normal. Within 5 days after surgery, tissue cGMP levels were increased by twofold in the abdominal testis. A fourfold elevation was noted from 10 to 30 days after surgery. Whereas the homogenate guanylate cyclase activity was only slightly elevated 10 and 20 days postoperatively, a 200% increase in the soluble guanylate cyclase activity was seen at 5 days. Between 10 and 30 days, the rise in activity was >250% (P < 0.01). An increase in soluble guanylate cyclase activity was noted when the data were expressed as per milligram protein, per milligram DNA or per whole testis. Conversely, particulate guanylate cyclase activity was reduced by 40% in the cryptorchid testis. Kinetic analysis of the soluble enzyme prepared from abdominal and scrotal testes yielded linear Line-weaver-Burke plots for both enzyme preparations with an identical K(m) for guanosine triphosphate, but a three-fold higher maximal velocity for the abdominal enzyme. When the soluble guanylate cyclases from both testes were mixed and assayed together, the activities were additive rather than exhibiting synergism or inhibition. These experiments indicate that the altered V(max) is not due to a transferable activator or inhibitor.An immunocytochemical technique was used to assess the cell type in which the alterations in cGMP metabolism occurred. Comparison of the scrotal and abdominal testes revealed that the abdominal testis exhibited enhanced cGMP immunofluorescence within the cells lining the inner aspect of the seminiferous tubule as well as tubular elements and interstitial cells. Thus, it is inferred that the correlated changes in soluble guanylate cyclase activity and cGMP levels occur in several of the cell types that remain viable within the cryptorchid testis.
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PMID:Tissue guanosine-3',5'-cyclic monophosphate levels and soluble guanylate cyclase activity: a positive correlation during unilateral cryptorchidism in the rat testis. 2 53

Guanylate cyclase activity has been studied in muscle of normal subjects and of patients suffering from muscular and neuromuscular diseases. In normal tissue a guanylate cyclase activity was found in both soluble and particulate fractions of homogenate. We found also that the kinetic analysis of the enzyme of soluble differed from that of particulate fraction. A decrease of guanylate cyclase activity in crude homogenate was observed in muscular dystrophies, in neuromuscular atrophies, and in inflammatory forms of muscle disease.
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PMID:Guanylate cyclase activity in normal and diseased human muscle. 2 81

1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by contaminating soluble enzyme, suggesting that physiological aggregating agents may increase cyclic GMP in intact platelets through the effects of intermediary factors. The activated and inhibited states of the enzyme described in the present paper may be relevant to the actions of these factors.
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PMID:Factors affecting the activity of guanylate cyclase in lysates of human blood platelets. 2 7

Purified prostaglandin endoperoxides (PGG2 and PGH2) and hydroperoxides (15-OOH-PGE2) as well as fatty acid hydroperoxides (12-OOH-20:4, 15-00H-20:4, and 13-OOH-18:2) were examined as effectors of soluble splenic cell guanylate cyclase activity. The procedures described (in the miniprint supplement) for the preparation, purification, and characterization of these components circumvented the use of diethyl ether which obscured effects of lipid effectors because of contaminants presumed to be ether peroxides which were stimulatory to the cyclase. Addition of prostaglandin endoperoxides or fatty acid hydroperoxides to the reaction mixture led to a time-dependent activation of guanylate cyclase activity; 2.5- to 5-fold stimulation was seen during the first 6 min. The degree of stimulation and rate of activation were dependent on the concentration of the fatty acid effector; when initial velocities (6 min) were assessed half-maximal stimulation was achieved in the range of 2 to 3 micrometer. However, by extending the incubation time to 90 min similar maximal increases in specific activity could be achieved with 3 or 10 micrometer PGG2 or PGH2. Activation of guanylate cyclase upon addition of prostaglandin endoperoxides or fatty acid hydroperoxides was prevented or reversed by the thiol reductants dithiothreitol (3 to 5 mM) or glutathione (10 to 15 mM). Na2S2O4, not known as an effective reducing agent of disulfides, prevented but was relatively ineffective in reversing activation after it had been induced by PGG2. Pretreatment of the enzyme preparation with increasing concentrations of N-ethylmaleimide in the range of 0.01 to 1.0 mM prevented activation by PGG2 without affecting basal guanylate cyclase activity. These observations indicate that fatty acid hydroperoxides and prostaglandin endoperoxides promote activation of the cyclase by oxidation of enzyme-related thiol functions. In contrast PGE2, PGF2a, hydroxy fatty acids (13-OH-18:2, 12-OH-20:4) as well as saturated (18:0) monoenoic (18:1), dienoic (18:2), and tetraenoic (20:4) fatty acids were ineffective in promoting cyclase activation in the range of 1 to 10 micrometer. Studies to identify the species of the rapidly metabolized prostaglandin endoperoxides that serve as effectors of the cyclase indicated that PGG2 but not 15-OOH-PGE2 (the major buffer-rearrangement product of PGG2) is most likely an activator. In the case of PGH2, a rapidly generated (30 s) metabolite of PGH2 was found which contained a hydroperoxy or endoperoxy functional group and was equally as effective as PGH2 as an apparent activator of the enzyme. The combined effects of PGG2 and dehydroascorbic acid, another class of activator, exhibited additivity with respect to the rate at which the time-dependent activation was induced. These results suggest that activation of soluble guanylate cyclase from splenic cells can be achieved by the oxidation of sulfhydryl groups that may be associated with specific hydrophobic sites of the enzyme or a related regulatory component.
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PMID:Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides. 2

Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.
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PMID:Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice. 3 Jan 19

Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61).
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PMID:[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy]. 3 Feb 12

The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored.
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PMID:Effect of hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine on guanylate cyclase activity. 3 Jun 19

The nucleotide cyclic GMP has been reported to be involved in cell proliferation and malignant transformation. Nitroso chemical carcinogens activate the enzyme guanylate cyclase (EC 4.6.1.2) which catalyzes the production of cyclic GMP. The present investigation demonstrates that compounds from other major classes of carcinogens including (1) alpha-halo ethers (chloromethyl methyl ether); (2) aromatic amines (benzidine and B-naphthylamine); (3) polycyclic hydrocarbons (1,2-benzanthracene and acridine); (4) azo dyes (p-dimethylaminoazobenzene), and (5) aflatoxins (B1, B2, G1, G2) produced a striking and significant inhibition of guanylate cyclase over a general concentration range of 0.5-13 mmol/1 in a variety of tissues. Some of the nitrosamides which increase guanylate cyclase activity, increase DNA synthesis whereas carcinogens which decrease guanylate cyclase activity inhibit DNA or RNA synthesis suggesting a relationship between cyclic GMP, DNA synthesis, and chemical carcinogenesis.
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PMID:Modulation of rat guanylate cyclase activity in vitro by chemical carcinogens. 3 Jun 21


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