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)

The postnatal development of mammalian skeletal muscle is associated with an increased capacity for glycogenolysis. In the present study rabbit skeletal muscle underwent a 7-fold increase in glycogen synthase and glycogen phosphorylase activity over the postnatal period of 0--8 weeks. An enriched fraction of sarcolemma was prepared from neonatal and adult muscle to examine the development of the beta-adrenergic receptor-adenylate cyclase system. Adult membranes possessed a 2-fold greater Na+K+(Mg2+)-ATPase activity and a 6--8 fold greater sodium fluoride- and epinephrine-stimulated adenylate cyclase activity. The activation ratio (effector activity/basal activity) increased 2--3 fold for epinephrine and sodium fluoride in adult sarcolemma. The activation by catecholamines conformed to the physiological beta 2 type response with isoproterenol (1.8 . 10(-8) M) > epinephrine (1.1 . 10(-7) M) > norinephrine (3.2 . 10(-6) M). In contrast, binding studies employing (-)-[3H]dihydroalprenolol showed little difference between neonatal and adult membranes with respect to (1) number of binding sites, (2) equilibrium dissociation constant and (3) displacement of (-)-[3H]dihydroalprenolol by catecholamine agonists. Protein and lipid components of the sarcolemma were also modified during development. Neonatal membranes possessed two glycopeptides of Mr 80000 and 86000, whereas in the adult only a single Mr 113000 species was evident. The total lipid phosphorus and phospholipid composition was unchanged during development. The content of linoleic acid increased approx. 3-fold during development in the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids. The cholesterol content of adult membranes was decreased by 29% compared to neonatal membranes.
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PMID:Beta-adrenergic receptor-adenylate cyclase alterations during the postnatal development of skeletal muscle. 625 11

The effects of epinephrine and electrical stimulation on lipolysis in the skeletal muscles of lean, and obese-diabetic (db/db) mice were studied using the perfused mouse hindquarter preparation. The rate of glycerol release from the obese mouse preparation was two times that of their lean littermates. Epinephrine sensitivity in the db/db mice was reduced only with respect to lipolytic activation, but was unaltered with respect to tissue cyclic AMP elevation and glycogen phosphorylase activation. Electrical stimulation caused a prompt increase in lactate production in both lean and obese mice and elevated glycerol release only in the obese mice. Glycerol release was also increased in the lean mice by stimulating at voltages exceeding 10 volts. Cyclic AMP levels were unaffected by electrical stimulation. Omission of calcium from the perfusion medium severely blunted lipolytic activation by electrical stimulation, which could be restored by calcium readdition. These results suggest that an impairment in lipolytic activation by epinephrine distal to activation of adenylate cyclase exists in the skeletal muscle of young db/db mice. Despite of this impairment, however, lipolysis in the obese mouse muscle was more sensitive to activation by electrical stimulation through a mechanism unrelated to changes in cyclic AMP, but is dependent on extracellular calcium.
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PMID:Activation of lipolysis by epinephrine and electrical stimulation in the perfused hindquarters of lean and obese-diabetic (db/db) mice. 630 33

We have studied the compartmentation of cyclic AMP action in purified ventricular cardiomyocytes prepared by collagenase perfusion of adult rabbit hearts. Incubation of purified adult myocytes with 1 microM isoproterenol causes rapid accumulation of intracellular cyclic AMP in both soluble (2.3 leads to 7.7 pmol/ mg of protein) and particulate (3.0 leads to 9.2) fractions of cell homogenates (3000 X g for 5 min), increases in the total activity and activity ratio of soluble cyclic AMP-dependent protein kinase (0.21 leads to 0.66), a decrease in protein kinase activity remaining in the particulate fraction (47 leads to 30%), and an increase in the activity ratio of glycogen phosphorylase (0.15 leads to 0.47). Incubation of myocytes with 10 microM prostaglandin E1 (PGE1) leads to a comparable increase in soluble cyclic AMP (2.3 leads to 5.8 pmol/mg of protein) and activation of soluble cyclic AMP-dependent protein kinase (0.21 leads to 0.39) but does not result in any change in cAMP or protein kinase in the particulate fraction and fails to cause an activation of glycogen phosphorylase. PGE1 does not inhibit the effects of isoproterenol; when myocytes are incubated with both isoproterenol and PGE1, the accumulation of cyclic AMP, activation of cAMP-dependent protein kinase and phosphorylase b leads to a conversion are equal to that achieved with isoproterenol alone. Perturbation of cellular calcium using the ionophore A23187, verapamil, or high or low extracellular calcium did not alter the ability of isoproterenol to cause activation of particulate cAMP-dependent protein kinase or influence the inability of PGE1 to do so. Activation of adenylate cyclase by forskolin (30 microM) caused immediate activation of both soluble and particulate cAMP-dependent protein kinase leading to rapid activation of phosphorylase. We conclude that the hormonally specific compartmentation of cyclic AMP and cAMP-dependent protein kinase that occurs in intact heart (Hayes, J. S., Brunton, L. L., Brown, J. H., Reese, J. B., and Mayer, S. E. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 1570-1574) is not explained on the basis of cellular heterogeneity but has a subcellular basis within the cardiomyocyte.
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PMID:Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes. 630 96

The cAMP-dependent enzymic system of glycogen phosphorolysis control was studied in the liver and myocardium of rats 2-168 h after tetrachloromethane single administration. It is shown that 2 h after the tetrachloromethane administration the content of cAMP in the rat liver rises and adenylate cyclase activity increases, which is accompanied by activation of phosphorylase b kinase, glycogen phosphorylase and a sharp fall in the content of glycogen; activation of phosphorylase a phosphatase is observed as well. No changes are found in the content of cAMP, glycogen and in the activity of glycogen phosphorylase in the myocardium. The tetrachloromethane effect disturbs the ratio between molecular forms of glycogen phosphorylase in the rat liver. There occurs a considerable shift towards prevalence of phosphorylase a as compared to phosphorylase b with the total amount of the enzyme (a + b) decreased.
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PMID:[cAMP-dependent regulation of glycogen phosphorolysis in rat liver after exposure to tetrachloromethane]. 631 53

Adipocytes can be readily isolated from intact adipose tissue. In adipocytes from hamster and human white adipose tissue it is possible to demonstrate beta, alpha 1, and alpha 2 adrenoceptors. Alpha 2 adrenoceptor activation inhibits while beta adrenoceptor activation stimulates cyclic AMP accumulation and lipolysis. The effects of catecholamines on cyclic AMP accumulation are mediated through regulation of adenylate cyclase activity, which is activated through beta adrenoceptors and inhibited through alpha 2 adrenoceptors. Activation of alpha 1 adrenergic receptors has been shown to be associated with elevations of cytosol calcium and increased turnover of phosphatidylinositol. In white adipocytes, the only known alpha 1 adrenergic effects are inhibition of glycogen synthase and stimulation of glycogen phosphorylase via mechanisms distinct from those by which cyclic AMP produces similar end effects. In brown adipocytes, alpha 1 adrenoceptor activation stimulates respiration. Thyroid hormones primarily regulate the sensitivity of adipocytes to beta-adrenergic amines while having little effect on alpha adrenoceptor sensitivity.
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PMID:Adrenergic regulation of adipocyte metabolism. 631 35

Hepatocytes isolated from normal and cholestatic rats responded to adrenergic agonists and antagonists in a quite different manner. Much greater activation of glycogen phosphorylase was caused by phenylephrine, an alpha-agonist, than by isoproterenol, a beta-agonist, in normal rat hepatocytes, and vice versa in the cholestatic rat cells. Epinephrine activation of phosphorylase was antagonized more efficiently by phenoxybenzamine, an alpha-antagonist, than by propranolol, a beta-antagonist, in normal rats, whereas it was antagonized totally by propranolol but only partially by phenoxybenzamine in cholestatic rat hepatocytes. The number of alpha-adrenergic receptors, measured by [3H]prazosin binding to membranes, as well as alpha-receptor-mediated increases in 32Pi incorporation into phosphatidylinositol and in 45Ca efflux, were reduced in hepatocytes after induction of cholestasis. The reduction of these parameters of alpha-receptor-linked functions was associated with the reciprocal increase in the number of beta-receptors and enhancement of beta-receptor-mediated accumulation of cyclic AMP in cholestatic rat hepatocytes. The affinity of epinephrine for beta-receptors was higher in cholestatic rat cells than in normal rat cells; this difference in affinity was abolished by the addition of guanylylimidodiphosphate, indicating that induction of cholestasis rendered hepatic beta-receptors more tightly coupled to the GTP-binding protein. Thus, the cascade reactions arising from beta-receptors are predominant over those from alpha-receptors, eventually leading to glycogen breakdown in cholestatic rat hepatocytes, principally because of not only the elevated beta to alpha ratio of the membrane receptor density but also the tight coupling of beta-receptors to the adenylate cyclase system via the guanine nucleotide regulatory protein.
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PMID:Predominance of beta-adrenergic over alpha-adrenergic receptor functions involved in phosphorylase activation in liver cells of cholestatic rats. 632 91

Radioligand binding studies identified two classes of 125I-angiotensin II-binding sites in rat liver membranes. High affinity binding sites (Kd = 0.35 +/- 0.13 nM, N = 372 +/- 69 fmol/mg of protein) were inactivated by dithiothreitol (0.1-10 mM) without any apparent change in low affinity binding sites (Kd = 3.1 +/- 0.8 nM, N = 658 +/- 112 fmol/mg of protein). Dithiothreitol inactivation was readily reversible but could be made permanent by alkylation of membrane proteins with iodoacetamide. Angiotensin II stimulation of glycogen phosphorylase in isolated rat hepatocytes (maximal stimulation 780%, EC50 = 0.4 nM) was completely inhibited by 10 mM dithiothreitol, a concentration which also abolished high affinity site binding; phosphorylase stimulation by glucagon and norepinephrine under these conditions was unaltered. Angiotensin II inhibition of glucagon-stimulated adenylate cyclase activity in hepatocytes required higher angiotensin II concentrations (EC50 = 3 nM) than phosphorylase stimulation and was not affected by dithiothreitol. Fractional occupancy of high affinity binding sites by 125I-angiotensin II correlated closely with angiotensin II-mediated phosphorylase stimulation, whereas occupancy of low affinity sites paralleled inhibition of adenylate cyclase activity. These data indicate that the physiologic effects of angiotensin II in rat liver are mediated by two distinct receptors, apparently not interconvertible, and provide the first evidence for angiotensin II receptor subtypes with differing biochemical features and mechanisms of action.
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PMID:Characterization of angiotensin II receptor subtypes in rat liver. 633 67

The administration of a single oral dose of DDT (150 mg/kg body wt.) to rhesus monkey elevated the hepatic glycogen and glycogen synthase activity but depressed the glycogen phosphorylase activity. A decrease in adenylate cyclase, both basal as well as fluoride and norepinephrine stimulated activity, was observed in liver of DDT-treated animals as compared to controls. Gluconeogenic enzymes did not record any significant change in the liver.
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PMID:Acute exposure of rhesus monkeys to DDT: effect on carbohydrate metabolism. 677 Oct 27

Space flight factors did not influence activity of glycogen phosphorylase and adenylate cyclase in skeletal muscles of rats. Activity of glucose-6-phosphate and 6-phosphogluconate dehydrogenases increased noticeably in the most active muscles (gastrocnemius and tibialis anterior muscles). Activation of enzymes involved in the pentosephosphate pathway of glucose conversion may be associated with compensatory processes induced by muscle changes due to diminished motor activity of animals in space flight.
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PMID:[Enzyme activity of carbohydrate metabolism in rat skeletal muscle after space flight]. 728 70

We report here our investigation of the role of cyclic AMP (cAMP) in amylin signal transduction in isolated strips of soleus muscle. Rat amylin, at 100 nM, increased cAMP levels, from 0.431 +/- 0.047 to a peak of 1.24 +/- 0.01 pmol cAMP/mg wet wt. after 5 min, in the absence of added phosphodiesterase inhibitor. The EC50 of the response was 0.48 nM (+/- 0.12 log units) in the absence of insulin and 0.3 nM (+/- 0.18 log units) in the presence of 7.1 nM insulin. The response seen with a maximally effective concentration of amylin (10 nM) was similar to that seen with a maximally effective concentration of epinephrine (1 microM) under the same conditions. Consistent with the observed rise in cAMP there was an increase in glycogen phosphorylase a (EC50 2.2 nM +/- 0.25 log units), decreased glycogen content (EC50 0.9 nM +/- 0.22 log units) and enhanced production of lactate (EC50 1.5 nM +/- 0.33 log units). These data support the concept that amylin promotes glycogenolysis in skeletal muscle and enhances production of lactate through glycolysis as a result of activation of Gs coupled receptors, stimulation of adenylate cyclase, elevation of cAMP levels and activation of glycogen phosphorylase.
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PMID:Dose-dependent elevation of cyclic AMP, activation of glycogen phosphorylase, and release of lactate by amylin in rat skeletal muscle. 754 30


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