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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the following genetical experiments, the cya gene in E. coli was shown to be involved in the synthesis of both cyclic AMP and cyclic GMP. First, all five independent cya-deficient mutants accumulated exceedingly low amounts of cyclic GMP. Second, the ability to form both cyclic AMP and cyclic GMP was simultaneously restored by transduction of an intact cya locus to one of the above cya-deficient mutants. Third, a spontaneous revertant from one of the above mutants regained the synthetic activity for cyclic GMP as well as for cyclic AMP. Fourth, the characteristic of a strain overproducing cyclic GMP was co-transduced with the cya locus. These results suggest that the synthesis of both cyclic GMP and cyclic AMP is mediated by the same enzyme, adenylate cyclase, Interestingly, a reciprocal effect of glucose starvation was observed on the accumulation of both cyclic nucleotides. The formation of cyclic AMP was greatly enhanced on glucose starvation, whereas that of cyclic GMP proceeded at a slower rate than in the presence of glucose. This effect was observed only in cells carrying normal cya and crp genes, but not in a cya-altered or a crp-deficient strain.
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PMID:A possible involvement of cya gene in the synthesis of cyclic guanosine 3':5'-monophosphate in E. coli. 19 53

The levels of glycogen and cyclic AMP, incorporation of glucose into glycogen and activities of glycogen synthetase and phosphorylase were determined in pancreatic islets isolated from genetically obese mice and their lean litter-mates. Islets from obese mice had elevated glycogen levels, increased phosphorylase activity and an increased amount of glycogen synthetase in the physiologically more effective I-form, indicating an increased turnover of glycogen. There was no significant difference in cyclic AMP levels between islets of lean and obese mice, but inhibition of phosphodiesterase or stimulation of adenyl cyclase increased cyclic AMP levels more in obese than in lean mouse islets, indicating a more rapid turnover of cyclic AMP in the former. It is suggested that cyclic AMP stimulated phosphorolytic breakdown of glycogen may be one of the mechanisms responsible for the increased insulin secretory response to glucose observed in islets from genetically obese mice.
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PMID:Glycogen metabolism and cyclic AMP levels in isolated islets of lean and genetically obese mice. 20 May 36

The present experiment was planned to verify the effect of calcium on adenyl cyclase in isolated human adrenal cells. Normal adrenal glands were obtained surgically from patients with primary aldosteronism and advanced breast cancer. Isolated adrenal cells were prepared by the modified Haning's method. They were incubated at 37C under a gas mixture of 95 percent O2: 5 percent CO2 in calcium-free Krebs-Ringer bicarbonate buffer solution containing 0.2 percent glucose and 0.5 percent fatty acid-free bovine serum albumin, to which various doses of CaCl2 or ACTH were added. Thirty minutes later, cyclic-AMP was measured by cyclic-AMP assay kit (The Radio-chemical Center, Amersham). 11-OHCS was estimated fluorometrically by the modified Silber's method after incubation for 2 hours. In the calcium-free incubation medium, productions of 11-OHCS and cyclic-AMP were negligible. In the concentration of 2.54 mM/L of calcium, 11-OHCS production increased with significant difference statistically, while the increase of cyclic-AMP production was not significant. In the concentration of 12.70 mM/L of calcium, however, cyclic-AMP production increased remarkably. When ACTH was added to the incubation medium containing 2.54 mM/L of calcium, productions of 11-OHCS and cyclic-AMP also increased remarkably. These results indicate that adenyl cyclase of human adrenocortical cells is directly stimulated by calcium and suggest that calcium acts as the second messenger of ACTH.
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PMID:[The effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)]. 20 11

Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.
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PMID:Adenosine as inhibitor of myocardial effects of catecholamines. 20 20

Enterotoxigenic Escherichia coli are associated with noninflammatory diarrhea and stimulate adenylate cyclase activity of mammalian cells, thereby increasing intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP). Increased concentrations of cyclic AMP in polymorphonuclear neutrophils (PMN) inhibit phagocytosis, candidacidal activity, granule discharge, and chemotactic responsiveness. We examined the effect of enterotoxin on the interaction of human PMN with E. coli. Enterotoxigenic and nonenterotoxigenic strains, including serotypes of E. coli identical except for the presence or absence of the plasmid coding for enterotoxin production, were utilized. Enterotoxigenic and nonenterotoxigenic E. coli, tumbled with PMN, were phagocytized and killed (>97%) equally well, and these strains stimulated PMN hexose monophosphate shunt activity equivalently.However, a chemotaxis assay under agarose demonstrated that filtrates of 10 enterotoxigenic strains were less chemotactic for PMN by 15+/-2% total migration or 46+/-1% directed migration, when compared with 6 non-enterotoxigenic strains (P < 0.001). Inactivation of the enterotoxin by heat (65 degrees C for 30 min) or antibodies formed to E. coli enterotoxin eliminated the inhibitory effect of the enterotoxic filtrates for PMN chemotaxis. Addition of purified E. coli enterotoxin directly to the PMN decreased chemotaxis to E. coli filtrates by 32+/-2% (P < 0.001). These data suggest that the effect was due to the heat-labile enterotoxin. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), which potentiates effects due to an increase in intracellular cyclic AMP, further decreased total PMN migration (random plus directed) toward enterotoxic filtrates to 46% of that to nonenterotoxic filtrates (P < 0.001). Addition of cholera toxin (1 mug/ml), which is similar to E. coli enterotoxin, to the PMN inhibited total migration toward nonenterotoxic filtrates by 16+/-2% (P < 0.001). Exogenous dibutyryl cyclic AMP (2 mM) inhibited total PMN migration toward E. coli filtrates by 32% (P < 0.001). PMN intracellular cyclic AMP levels increased by 220% after 2 h of incubation with purified E. coli enterotoxin. The decreased chemotactic attractiveness of enterotoxic E. coli filtrates appears to be related to the ability of enterotoxin to increase cyclic AMP in PMN. Enterotoxin production by E. coli may be advantageous to the microbe by decreasing its chemotactic appeal for PMN.
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PMID:Interaction of polymorphonuclear neutrophils with Escherichia coli. Effect of enterotoxin on phagocytosis, killing, chemotaxis, and cyclic AMP. 20 10

Incubation of raty erythrocytes and reticulocytes in Tris-Ringer's medium with 5 mM cyclic-AMP or AMP increased lactate formation and glucose utilization. The glycolysis-stimulating effect of cyclic-AMP is very similar to that of AMP and, in both cases, it seems to be higher in reticulocytes than in erythrocytes. 0.5 mM norepinephrine produced a much higher lactate formation in reticulocytes than in erythrocytes, suggesting a greater adenylate cyclase activity in younger cells. 300 micrometer cyclic-AMP and AMP reverse inhibition produced by ATP (up to 1.5 micrometer) on phosphofructokinase from rat reticulocyte haemolysates. Both nucleotides are positive allosteric effectors of the enzyme as shown by displacement of F6P-saturation curve to hyperbolic kinetics. Similar results were previously obtained with rat erythrocytes. This deinhibitory effect is suggested to be responsible of the above glycolysis-stimulating effect.
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PMID:Comparative activation by AMP and cyclic-AMP of rat erythrocyte and reticulocyte glycolysis. 20 50

We have found evidence that transcription of the galactokinase (ATP:D-galactose 1-phosphotransferase; EC 2.7.1.6) gene is inhibited, in the animal-like protozoan Tetrahymena, by dibutyryl adenosine 3':5'-cyclic monophosphate, glucose, and epinephrine. The specific activities of galactokinase in Tetrahymena cells grown in defined media with galactose or glycerol as the principal carbon source are equivalent; the specific activity in glucose minimal medium is [unk] the value. Thus, while there seems to be no specific induction of the enzyme by the substrate, galactose, there is a strong "repression" by glucose. This repression by glucose is mimicked, in glycerol-grown cells, by the addition of millimolar amounts of dibutyryl adenosine 3':5'-cyclic monophosphate or phosphodiesterase inhibitors such as caffeine and theophylline. When glucose-grown cells are washed and resuspended in carbohydrate-free medium, the galactokinase specific activity increases by as much as 10-fold within 12 hr. This increase is blocked by dibutyryl adenosine 3':5'-cyclic monophosphate and by epinephrine (synthesized by Tetrahymena, and previously shown to activate a membrane-bound adenylate cyclase in extracts of this organism), as well as by inhibitors of mRNA synthesis, maturation, and translation. Our results suggest that glucose and epinephrine can regulate transcription of the galactokinase gene by modulation of cyclic nucleotide levels. The observation that the nonmetabolized sugars 2-deoxyglucose, 2-deoxygalactose, and alpha-methylglucoside are as effective as glucose suggests that the sugar itself, or an immediate metabolite such as the 1-phosphate derivative, may be the effector.
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PMID:Genetic regulation of galactokinase in Tetrahymena by cyclic AMP glucose, and epinephrine. 20 71

Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation. In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming. It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic "memory" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release.
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PMID:Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action. 20 21

The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media. The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period. Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs. Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished. It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin.
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PMID:Interacting effects of sulfonylureas and glucose on cyclic AMP metabolism and insulin release in pancreatic islets of the rat. 20 36

Muscle and blood metabolites, plasma insulin and cyclic adenosine 3',5'-monophosphate (cAMP) levels were investigated in five male runners before and after strenuous intermittent running exercise of short duration. Immediately after the exercise, the mean muscle creatine phosphate level (CrP) had fallen by 74% (P less than 0.02) and 30 min later the initial level was regained in only one subject. Other immediate results were increases in mean muscle lactate (460%, P less than 0.005), glucose (130%), glucose-6-phosphate (G6P, 320%) and fructose-1,6-diphosphate (FDP, 32%). Muscle ATP and glycogen concentration had decreased by 31 and 23% (P less than 0.05), respectively. However, ATP, glucose, G6P and FDP changes were not significant owing to the great individual variation. This may have been due to the different training programmes of the runners. Immediately after the exercise mean plasma insulin was 210% (P less than 0.01), blood glucose 71% (P less than 0.005) and plasma cAMP concentration 260% (P less than 0.01) higher than the pre-exercise values. After running urinary excretion of cAMP was 29% higher than before the exercise. It is concluded that exhaustive, short-term exercise activates the liver adenylate cyclase system so giving rise to an increased level of blood glucose, which is an important source of energy during this type of exercise.
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PMID:Muscle metabolism during and after strenuous intermittent running. 21 Apr 97


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