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)

Binding of [3H] epinephrine to plasma membrane-enriched fractions from guinea pig heart and rabbit skeletal muscle was investigated using the micropore filtration technique. [3H] Epinephrine and [3H] norepinephrine were found to be degraded rapidly in aqueous buffer at pH 7.6 and 37 degrees C. Deterioration of the compounds could be prevented by low concentrations of dithiothreitol. Binding of [3H] epinephrine to both membrane preparations was a slow process requiring 60 min to approach equilibrium in the case of cardiac membranes at 37 degrees C, and 20 min for skeletal muscle membranes at 0 degrees C. Binding was antagonized by the unlabeled beta agonists, isopropylnorepinephrine, epinephrine, and nor epinephrine; each was equipotent, in contrast to their different potency is eliciting beta-adrenergic responses and in stimulating adenylate cyclase. A variety of catechol compounds were as effective as antagonists of binding as the catecholamines. Methylation of one ring hydroxyl abolished inhibitory activity. The beta-adrenergic antagonists, propranolol, pronethalol, and dichlorisoproterenol, were not effective in inhibiting binding to either membrane preparation. D-Norepinephrine and L-norepinephrine were equieffective in antagonizing binding of [3H] norepinephrine to skeletal muscle membranes, suggesting that binding was not stereospecific. These and other data led to the conclusion that binding of labeled catecholamine to isolated tissue membranes using the micropore filtration technique probably does not reflect interaction with the specific beta-adrenergic recptor, but more likely reflects a less specific binding of compounds with one or more hydroxyl groups on a ring.
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PMID:Adenylate cyclase and catecholamine binding in plasma membrane-enriched preparations of cardiac and skeletal muscle. 17 93

The method of Kidwai et al. (1971. Biochem. Biophys. Res. Commun. 45:901) offers a rapid and simple technique for the preparation of membrane fractions from rat heart, using sucrose density centrifugation of a 100,000x g pellet. We have investigated the distribution of adenylate cyclase, cyclic AMP phosphodiesterase, and norepinephrine binding activity in these fractions. Specific activity of adenylate cyclase was high in the plasma membrane (PM) and sarcoplasmic reticulum, as well as the nuclear (N) fractions, but 80-90 percent of the total activity was found in the N fraction. Epinephrine stimulation of adenylate cyclase was present in all fractions but did not exceed 25 percent of basal activity. The activity in the mitochondrial fraction was low and insensitive to epinephrine. About 10 percent of phosphodiesterase activity was found in the 100,000 x g pellet. After density gradient centrifugation, 70 percent of this portion was recovered in the N fraction, with the highest specific activity present in the PM fraction. Binding of [3H] norepinephrine was measured by a membrane filtration technique. Binding activity was found in all fractions, and it paralleled roughly the distribution of adenylate cyclase. However, only about 25-30 percent of the binding was blocked by propranolol, except in the PM fraction where binding was not prevented by this drug. Further, a comparison of adenylate cyclase activities with norepinephrine binding yields a turnover number for the enzyme of the order of 10(-2) sec-1, assuming a 1:1 relationship between beta-adrenergic recptor and adenylate cyclase. Since this value seems unrealistic, we suspect that either the binding activity measured is unrelated to the beta-adrenergic receptor or the receptor to cyclase ratio is considerably larger than unity.
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PMID:Adenylate cyclase, cyclic nucleotide phosphodiesterase, and norepinephrine binding in rat heart membranes. 17 94

Protein kinase, phosphodiesterase and adenylate cyclase of plasma membrane of adipocytes and the effect of the feedback regulator (FR) on these three enzymes was measured and compared. The basal level ratio of adenylate cyclase to phosphodiesterase to protein kinase was 1:1.9:3.0. Epinephrine and/or FR alters this ratio. FR stimulated protein kinase activity up to 3 fold in the presence of a wide range of enzyme concentrations, 5-50 mug membrane protein/tube. The concentration of FR effective for stimulation of membrane protein kinase was much greater than that needed for inhibition of adenylate cyclase and phosphodiesterases. The inhibition by FR on adenylate cyclase was the most potent effect among the 3 enzymes. 1 U (or 2 U/ml) of FR inhibited 50% of the adenylate cyclase activity in a defined system. The maximum effective concentration of FR for stimulation of membrane protein kinase was greater than 10 U/ml. Histone type 11A was the best substrate for protein phosphorylation so far observed. The FR stimulatory effect was observed at all substrate concentrations used ranging from 1-5 mg/ml. A NaF concentration curve shows that 15 mM NaF gave maximum phosphorylation. The stimulatory effect of FR was observed both in the presence and absence of NaF. Protein kinase of adipocyte plasma membrane was mainly cAMP-independent. The effect of FR (20 U/ml) in stimulation of protein phosphorylation was much greater than that of cAMP (1 X 10(-6) M). The cAMP and FR effects seemed to be additive. Preincubation of plasma membrane with FR in the absence of ATP resulted in no decrease but slight increase in protein kinase activity. A shift in protein kinase, phosphodiesterase and adenylate cyclase ratios by FR suggests the regulatory role of FR in cAMP metabolism in adipocytes.
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PMID:Influence on adipocyte plasma membrane bound protein kinase by feedback regulator. 17 96

The compound N-[2-hydroxy-3-(1-naphthoxy)-propyl]-N'-bromoacetylethylenediamine (NHNP-NBE) was found to label covalently the beta-adrenergic receptor in turkey erythrocytes. The compound inhibits irreversibly 1-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the whole turkey erythrocyte as well as in the erythrocyte membranes possessing the beta-receptor. The affinity label blocks, also irreversibly, the specific [3H] propranolol binding, whereas other bromoacetyl compounds tested have no effect on binding, even at high concentrations, which cause enzyme inactivation. 1-Epinephrine and propranolol offer protection against the affinity label in whole turkey erythrocytes as well as in membranes prepared from these cells. The potential usefulness of an irreversible beta-antagonist is discussed.
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PMID:Affinity label for beta-adrenergic receptor in turkey erythrocytes. 18 May 28

Adenosine triphosphatase (ATPase) activity in erythrocyte membranes from patients with Duchenne dystrophy was inhibited by ouabain less than in normal individuals in assay systems containing high or low contents of salt. Epinephrine and cyclic adenosine monophosphate increased total ATPase activity in all samples, and epinephrine restored ouabain sensitivity to the Duchenne membranes. Basal adenyl cyclase activity in about twice that of controls. Epinephrine stimulated adenyl cyclase activity of normal membranes two to three times, but did not stimulate the enzyme in Duchenne membranes. These differences may reflect a genetic abnormality of the membrane.
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PMID:Biochemical abnormalities of erythrocyte membranes in Duchenne dystrophy. Adenosine triphosphatase and adenyl cyclase. 18 Sep 37

1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.
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PMID:Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo. 18 27

Cyclic AMP levels and adenylate cyclase and phosphodiesterase activities were measured in control and ovalbumin-sensitized guinea pig lungs. Cyclic AMP levels were raised by epinephrine (0.01-10 mug/ml) in both control and sensitized lungs; the response being larger in the former group. Epinephrine (10(-9) -10(-6) M) stimulated adenylate cyclase in sensitized but had only a minimal effect in control preparations. Phosphodiesterase activities were equal in both groups. The hypersensitivity of adenylate cyclase response to epinephrine concurrent with diminished accumulation of cyclic AMP in sensitized guinea pigs indicate that antigen sensitization alters the response of the cyclic AMP system to epinephrine.
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PMID:Effect of epinephrine on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in control and antigen-sensitized guinea pig lungs. 19 Jun 22

The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.
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PMID:Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats. 19 69

The cyclic AMP metabolism of cultured epithelial cells was investigated. Epinephrine or 1-methyl,3-isobutylxanthine (MIX) alone had no effect on cyclic AMP levels in intact cells, whereas the combination of the two agents yielded a 6- to 10-fold increase in cyclic AMP levels. Both basal and stimulated cyclic AMP levels decreased with increasing cell density. Cell-free adenylate cyclase preparations were stimulated markedly by epinephrine or isoproterenol in the absence of MIX. Since the epithelial cells were found to have a relatively small amount of cyclic nucleotide phosphodiesterase (PDE) activity, the requirement for MIX to visualize intact cell responsiveness to epinephrine could be explained only partially by its PDE inhibitory properties.
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PMID:Adenylate cyclase activity in cultured epithelial cells. 19 55

Epinephrine injected intradermally activated pig skin adenylate cyclase and increased the epidermal cyclic AMP level in vivo. This biphasic response reached a maximum in 5 min and gradually decreased thereafter. The simultaneous injection of a cyclic AMP phosphodiesterase inhibitor, isobutyl methyl xanthin (IBMX) potentiated the increase. The simultaneous injection of a specific beta-adrenergic receptor inhibitor, propranolol, inhibited this accumulation of cyclic AMP. After the first activation by epinephrine in vivo, there was a marked refractoriness of the skin (epidermal) adenylate cyclase to subsequent epinephrine stimulation vivo and in vitro. This refractoriness was specific for catecholamine stimulation as responses to histamine were normal. Recovery from refractoriness started at 48 hr and was completed at 1 week after the injection of epinephrine.
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PMID:Epinephrine activation of pig skin adenylate cyclase in vivo and subsequent refractoriness to activation. 20 8


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