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)

Human adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) has been studied in preparations of fat cell membranes ("ghosts"). As reported earlier, under ordinary assay conditions (1.0 mM ATP, 5 mM Mg2+, 30 degrees C, 10 min incubation) the enzyme was activated 6-fold by epinephrine in the presence of the GTP analog, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P] (Cooper, B. et al. (1975) J. Clin. Invest. 56, 1350-1353). Basal activity was highest during the first 2 min of incubation then slowed and was linear for at least the next 18 min. Epinephrine, added alone, was often without effect. but sometimes maintained the initial high rate of basal activity. GMP-P(NH)P alone produced inhibition ("lag") of basal enzyme early in the incubation periods. Augmentation of epinephrine effect by GMP-P(NH)P, which also proceeded after a brief (2 min) lag period, was noted over a wide range of substrate (ATP) concentrations. GTP inhibited basal levels of the enzyme by about 50%. GTP also allowed expression of an epinephrine effect, but only in the sense that the hormone abolished the inhibition by GTP. Occasionally a slight stimulatory effect on epinephrine action was seen with GTP. At high Mg2+ concentration (greater than 10 mM) or elevated temperatures (greater than 30 degrees C) GMP-P(NH)P alone activated the enzyme. Maximal activity of human fat cell adenylate cyclase was seen at 50 mM Mg2+, 1.0 mM ATP, pH 8.2, and 37 degrees C in the presence of 10(-4) M GMP-P(NH)P; under these conditions addition of epinephrine did not further enhance activity. Human fat cell adenylate cyclase of adults was insensitive to ACTH and glucagon even in the presence of GMP-P(NH)P.
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PMID:Human fat cell adenylate cyclase. Enzyme characterization and guanine nucleotide effects on epinephrine responsiveness in cell membranes. 0 40

Rabbit heart membranes possessing the adenylate cyclase activity were isolated and purified by extraction with high ionic strength solutions and centrifugation in the sucrose density gradient. It was shown that the membranes are characterized by a high percentage of cholesterol (molar ratio cholesterol/phospholipids is 0.24) and an increased activity of Na, K-ATPase, which suggests the localization of adenylate cyclase in the sarcolemma. During centrifugation in the sucrose density gradient the activities of andenylate cyclase and Na,K-ATPase are not separated. Treatment of heart sarcolemma with a 0.3% solution of lubrol WX results in 10--20% solubilization of adenylate cyclase. Purification of the enzyme in the membrane fraction is accompanied by a decrease in the activity of phosphodiesterase; however, about 2% of the heart diesterase total activity cannot be removed from the sarcolemma even after its treatment with 0.3% lubrol WX. Epinephrine and NaF activate adenylate cyclase without changing the pH dependence of the enzyme. The alpha-adrenergic antagonist phentolamine has no effect on the adenylate cyclase activation by catecholamines, glucagon and histamine; the beta-adrenergic antagonist alprenolol competitively inhibits the effects of isoproterenol, epinephrine and norepinephrine, having no effect on the enzyme activation by glucagon and histamine. There is no competition between epinephrine, glucagon and histamine for the binding site of the hormone; however, there may occur a competition between the hormone receptors for the binding to the enzyme. A combined action of several hormones on the membranes results in the averaging of their individual activating effects. When the hormones were added one after another, the extent of adenylate cyclase activation corresponded to that induced by the first hormone; the activation was insensitive to the effect of the second hormone added. It is assumed that the outer membrane of myocardium cells contains a adenylate cyclase and three types of receptors, each being capable to interact with the same form of enzyme. The activity of adenylate cyclase is determined by the type of the receptor, to which it is bound and by the amount of the enzyme-receptor complex.
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PMID:[Isolation, purification and characterization of regulatory properties of adenylate cyclase from rabbit heart]. 2 49

It has been shown that the activity of Ca(2+)-ATPase increases during development. Epinephrine in vivo increases the activity of Ca(2+)-ATPase in chick skeletal muscles. The effect of hormone is lacking at embryonic stages of development and appears only before hatching. In the presence of exogenous protein kinase, cAMP also increases the activity of the enzyme, this effect being observed also in embryonic muscles. Lack of effect of epinephrine on Ca(2+)-ATPase in embryonic muscles is associated with non-reactivity of their adenylate cyclase to catecholamines. Ca(2+)-ATPase itself already at embryonic period is ready to react to cAMP. It is concluded that Ca(2+)-ATPase of sarcoplasmic reticulum is one of the sites of action of catecholamines on calcium metabolism in muscle cell and that this action is realized via the system adenylate cyclase-cAMP-protein kinase.
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PMID:[The effect of catecholamines on the Ca2(+)-adenosinetriphosphatase of the sarcoplasmic reticulum in the skeletal muscles in chicken ontogeny]. 9 34

A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1 plus 20 mM KC1. This increment, the Na, K-ATPase, was abolished by 10-5M ouabain, the K1 for ouabain being approximately 3 X 10-7M. 1-Epinephrine had no effect on Na, K-ATPase, but NaF was inhibitory. Adenylate cyclase, which had a basal activity of approximately 50% by NaC1 or KC1 alone at concentrations up to 0.2M. There was no additional stimulation of adenylate cyclase activity when na+ K+ included together. Both 1-epinephrine and NaF cause significant stimulation of adenylate cyclase, but neither basal nor activated cyclic AMP PRODUCTION WAS INFLUENCED BY OUABAIN. Half-maximal stimulation was seen at approximately 5 X 10-6M 1-epinephrine. Both the catecholamine and NaF increased the V-max ofcardiac plasma membrane adenylate cyclase without significantly influencing Km. Increasing Ca2+ in the range between 10-7 and 10-3M inhibited basal, 1-epinephrine-stimulated, and NaF-stimulated activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was 1-epinephrine stimulation was increased from approximately 60% in 0.5 mM EGTA to approximately 150% in 10-7M Ca2+ and 400% in 10-5M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feed back mechanism by which elevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.
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PMID:Control of cardiac sarcolemmal adenylate cyclase and sodium, potassium-activated adenosinetriphosphatase activities. 12 80

Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.
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PMID:Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h). 16 85

Adrenal cAMP and plasma corticosterone levels were determined in pre-weanling rats subjected to treatment with either ACTH (50 mU/rat) or histamine dihydrochloride (0.2 mg/g body wt). ACTH injection elevated both serum corticosterone and adrenal cAMP levels on all days tested. However, the ACTH-induced elevation of adrenal cAMP and serum corticosterone both diminished steadily from day 2 to day 8 and then increased from day 8 to day 16. Histamine injection resulted in elevated serum corticosterone levels in a pattern similar to that of the corticosterone response to ACTH. However, histamine injection did not result in any significant increase in adrenal cAMP from day 2 to day 10. From day 12 to day 16 the adrenal cAMP concentration rose steadily in parallel with ther serum corticosterone levels. These results indicate: (1) that a functional, ACTH-sensitive adenyl cyclase system is present in the adrenal gland of the immature rat, (2) that the responsiveness of this system diminishes during the first postnatal week before returning to its previous 2-day-old capacity by day 16, and (3) that during the first few days after birth, histamine stress results in elevated serum corticosterone levels without elevating adrenal cAMP levels.
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PMID:Effect of ACTH and histamine stress on serum corticosterone and adrenal cyclic AMP levels in immature rats. 16 40

Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.
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PMID:Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle. 16 62

Epinephrine infusion, 5-percent oxygen breathing, and splenic nerve stimulation were employed to increase cardiac output by 50-100% in anesthetized dogs. Epinephrine infusion as expected, increased plasma and myocardial cyclic AMP concentrations. Arterial hypoxemia increased cyclic AMP concentration in plasma but not in the heart. Practolol pretreatment abolished the increase in plasma cyclic AMP concentration and reduced the rise in cardiac output during hypoxemia. Splenic nerve stimulation was not associated with increases in either plasma or myocardial cyclic AMP. Adenylate cyclase activity was increased by addition of plasma into the incubation medium. However, splenic venous plasma obtained during splenic nerve stimulation did not increase adenylate cyclase activity more than control plasma obtained before stimulation. We conclude that the positive inotropic action of arterial hypoxemia and splenic nerve stimulation does not depend on the adenylate cyclase-cyclic AMP system.
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PMID:Effects of arterial hypoxemia and splenic nerve stimulation on myocardial adenosine 3',5'-Monophosphate in dogs. 16 96

Glucagon can stimulate gluconeogenesis from 2 mM lactate nearly 4-fold in isolated liver cells from fed rats; exogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP) is equally effective, but epinephrine can stimulate only 1.5-fold. Half-maximal effects are obtained with glucagon at 0.3 nM, cyclic AMP at 30 muM and epinephrine at 0.2 muM. Insulin reduces by 50% the stimulation by suboptimal concentrations of glucagon (0.5 nM). A half-maximal effect is obtained with 0.3 nM insulin (45 microunits/ml). Glucagon in the presence of theophylline (1 mM) causes a rapid rise and subsequent fall in intracellular cyclic AMP with a peak between 3 and 6 min. Some of the fall can be accounted for by loss of nucleotide into the medium. This efflux is suppressed by probenecid, suggesting the presence of a membrane transport mechanism for the cyclic nucleotide. Glucagon can raise intracellular cyclic AMP about 30-fold; a half-maximal effect is obtained with 1.5 nM hormone. Epinephrine (plus theophylline, 1 mM) can raise intracellular cyclic AMP about 2-fold; the peak elevation is reached in less than 1 min and declines during the next 15 min to near the basal level. Insulin (10 nM) does not lower the basal level of cyclic AMP within the hepatocyte, but suppresses by about 50% the rise in intracellular and total cyclic AMP caused by exposure to an intermediate concentration of glucagon. No inhibition of adenylate cyclase by insulin can be shown. Basal gluconeogenesis is not significantly depressed by calcium deficiency but stimulation by glucagon is reduced by 50%. Calcium deficiency does not reduce accumulation of cyclic AMP in response to glucagon but diminishes stimulation of gluconeogenesis by exogenous cyclic AMP. Glucagon has a rapid stimulatory effect on the flux of 45Ca2+ from medium to tissue.
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PMID:Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats. 16 37

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62


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